Administration of oral corticosteroids and/or azole antifungals for 4-6 months remains the standard treatment for allergic bronchopulmonary aspergillosis (ABPA). This study investigated the clinical characteristics of patients with difficult-to-treat ABPA who failed to achieve clinical remission within 6 months.

Among the participants of a nationwide survey conducted in Japan in 2020, treatment-naïve patients with ABPA who satisfied Asano's criteria were enrolled in this study. Clinical remission was defined as stable disease without exacerbation for ≥ 6 months under minimal treatment (oral prednisolone: ≤ 5 mg/day and no antifungal medication). A risk prediction score for difficult-to-treat ABPA was developed and validated in an independent cohort comprising patients with ABPA from a prospective registration study in Japan.

In total, 316 treatment-naïve patients with ABPA were enrolled in the study. The median time to minimal treatment status was 4.8 months in the group receiving standard treatment. The clinical remission rate at 6 months after standard treatment was 51%. Age ≤ 50 years at onset of ABPA (p = 0.04), serum A. fumigatus-specific IgE titer of ≥ 20 UA/mL (p = 0.006), positive culture for Aspergillus spp. in the sputum/bronchial lavage fluid (p = 0.05), and presence of high attenuation mucus (HAM; p = 0.10) were associated with difficult-to-treat ABPA. The number of positive indicators indicated the risk of failure of standard treatment to yield clinical remission within 6 months in the derivation (n = 87, p < 0.001) and validation (n = 64, p = 0.009) cohorts.

Multiple components, including age at onset, allergic sensitization, airway fungal burden, and HAM, were associated with difficult-to-treat ABPA.

The impact of bronchiectasis severity on the outcomes of patients with allergic bronchopulmonary aspergillosis (ABPA) remains uncertain.

To evaluate whether bronchiectasis severity is associated with an increased risk of ABPA exacerbations.

We retrospectively analyzed patients with ABPA between 2007 and 2019. Patients were categorized based on the segments involved by bronchiectasis as mild (1-5), moderate (6-9), and extensive (≥10). We compared lung function and immunological markers among the groups. A multivariable Poisson regression analysis, using follow-up duration as an offset variable, assessed the association between bronchiectasis severity and ABPA exacerbations, adjusting for key confounders. We report the association as an adjusted relative rate (aRR) with 95% confidence intervals (CI).

We included 705 patients with ABPA (mean age, 35 years). Of these, 219 (31.1%), 226 (32.1%), and 260 (36.9%) had mild, moderate, and extensive bronchiectasis, respectively. Patients with extensive bronchiectasis had poorer lung function and elevated immunological markers (serum total IgE, Aspergillus fumigatus-IgE, and A. fumigatus-IgG) than those with mild or moderate bronchiectasis. The exacerbation frequency increased with the severity of bronchiectasis (mild: 41.5% vs moderate: 53.4% vs extensive: 57.7%, P = .005). On multivariable analysis, the risk of ABPA exacerbation increased significantly with bronchiectasis severity (aRR [95% CI]; extensive: 1.51 [1.09-2.08], moderate: 1.50 [1.09-2.08]). In addition, increasing age (aRR, 0.84 [95% CI, 0.76-0.94]) and body mass index (aRR, 0.97 [95% CI, 0.94-0.99]) were associated with lower exacerbation risk after adjusting for total IgE, lung function, and high-attenuation mucus.

Moderate-to-extensive bronchiectasis is associated with worse lung function, heightened immunological severity, and an increased risk of ABPA exacerbation.

Allergic fungal rhinosinusitis (AFRS) is a unique endotype of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite high recurrence rates and often more severe presenting signs compared with other subtypes of CRSwNP, research dedicated to AFRS has been lacking. Diagnostic criteria are outdated, the mechanistic relationship of AFRS to other associated diseases is unclear, and the pathophysiology of disease and risk factors for recurrence have not been well studied. In December 2023, a multidisciplinary group of rhinologists, otolaryngologists, pulmonologists, allergists, immunologists, scientists, and infectious disease experts met at the National Institute of Health to discuss unmet needs for future AFRS research and care, including patient management, diagnostic criteria, severity, pathophysiology, and related conditions. A summary of these clinical and associated research discussions is included below.

Some studies of community-acquired pneumonia (CAP) have reported that human rhinovirus (HRV) is the most common virus in viral pneumonia in immunocompetent adults. Secondary bacterial and fungal infections are increasingly recognized complications of HRV infection that have substantial morbidity and mortality. We report a novel case of a co-infection of Streptococcus pneumoniae (S. pneumoniae) associated with HRV pneumonia that had successful diagnosis with combined target next generation sequencing (NGS) and percutaneous lung puncture biopsy (PLPB).

A 62-year-old female was admitted with productive cough, dyspnea and respiratory failure. She was initially diagnosed with severe pneumonia caused by HRV infection by targeted NGS from bronchial-alveolar lavage fluid. After initial clinical improvement treated by high flow nasal cannula (HFNC) and antibiotics, the patient's condition worsened again after her discharge, with persistent dyspnea and refractory hypoxemia. Chest computed tomography showed areas of consolidation and ground glass opacification. Despite empirical antibiotics for a suspected secondary co-infection, her condition showed no significant improvement. A PLPB was performed, and targeted NGS for the lung tissue was positive only for S. pneumoniae. Targeted NGS of her sputum was positive for S. pneumoniae, Aspergillus fumigatus and type A HRV. The patient was treated with linezolid, voriconazole and methylprednisolone. HFNC was weaned on day 57, and she was discharged with good lung recovery.

Our case demonstrates the diagnostic utility of combined targeted NGS and CT-guided PLPB in resolving refractory pneumonia with overlapping viral and bacterial etiologies. Co-infection with these two pathogens should be considered in the differential diagnosis of patients with consolidation, wheezing and respiratory failure following severe HRV infection. The combination of targeted NGS and CT-guided PLPB should be reserved for diagnostically challenging cases refractory to conventional methods.

Aspergillus species cause diverse clinical manifestations in bronchiectasis including allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS), and raised IgG indicating exposure to, or infection with, Aspergillus.

What are the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis?

Patients with bronchiectasis enrolled into the European Bronchiectasis Registry from 2015 through 2022 with laboratory testing for Aspergillus lung disease (total IgE, IgE specific to Aspergillus or Aspergillus skin test, or IgG specific to Aspergillus and blood eosinophil counts) were included for analysis. Modified International Society for Human and Anima Mycology ABPA working group criteria (2024) were used to define ABPA.

Nine thousand nine hundred fifty-three patients were included. Six hundred eight patients (6.1%) were classified as having ABPA, 570 patients (5.7%) showed AS, 806 patients (8.1%) showed raised Aspergillus-specific IgG without AS, 184 patients (1.8%) showed both AS and had raised Aspergillus-specific IgG levels, and 619 patients (6.2%) demonstrated eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72% showed negative Aspergillus serologic findings. Patients with ABPA, AS, or raised Aspergillus-specific IgG demonstrated more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG experienced higher exacerbation frequency and more severe exacerbations. AS was associated with increased exacerbations and hospitalizations only in patients not receiving inhaled corticosteroids.

Aspergillus lung disease is common in bronchiectasis. Raised IgG levels to Aspergillus were associated with significantly worse outcomes, whereas ABPA and AS were associated with severe disease and exacerbations with a risk that is attenuated by inhaled corticosteroid use.

Pulmonary aspergillosis is a major global health concern, yet its diagnosis remains challenging. Aspergillus-specific IgG measurement is essential for identifying chronic and allergic forms.

This study aimed to evaluate a quantitative method, the ImmunoCAP assay IgG m3 (ICAP) (Phadia-ThermoFisher Scientific, Waltham, USA), a qualitative method, the Aspergillus IgG Western blot kit (Asp-WB) (LDBio Diagnostics, Lyon, France) and a combination of both methods for the diagnosis of Aspergillus lung disease.

A retrospective study was conducted at the University Hospital of Marseille, France, during 1 year. Patients undergoing Aspergillus serology were divided into three groups: Group 1 (G1) with ICAP ≥ 40 mgA/L and positive Asp-WB, Group 2 (G2) with ICAP ≥ 40 mgA/L and negative Asp-WB and Group 3 (G3) with ICAP < 40 mgA/L and positive Asp-WB. Data were collected on demographics, underlying diseases, imaging and biological outcomes. Patients were classified according to their Aspergillus lung disease, whether acute pulmonary aspergillosis, chronic pulmonary aspergillosis (CPA), allergic broncho-pulmonary aspergillosis (ABPA), colonisation or Aspergillus sensitisation.

A total of 536 patients were studied: 173 in G1, 204 in G2 and 200 in G3, with 38 patients found in several groups. The primary underlying disease was cystic fibrosis in 44.6% of patients. Twenty-two patients were diagnosed with ABPA. The number of diagnosed ABPA cases in G1 (20; 11.6%) combining positive ICAP and Asp-WB was significantly higher than that found in the groups with a single positive test result (p < 0.001). Fifteen patients were diagnosed with CPA. Isolated positive Western blot (G3) identified five cases of aspergilloma. Significantly fewer Aspergillus lung diseases were diagnosed in isolated positive ICAP G2 (8.8%) than in G1 (53.8%) and G3 (42.5%) (p < 0.001).

This study highlights the benefits of combining Asp-WB and ICAP for the diagnosis of Aspergillus lung disease and the relatively high false-positive rate in patients with isolated positive ICAP results.

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.

Cystic fibrosis is a severe, inherited, life-limiting disorder, and over half of those living with CF are children. Persistent airway infection and inflammation, resulting in progressive lung function decline, is the hallmark of this disorder. Aspergillus colonization and infection is a well-known complication in people with CF and can evolve in a range of Aspergillus disease phenotypes, including Aspergillus bronchitis, fungal sensitization, and allergic bronchopulmonary aspergillosis (ABPA). Management strategies for children with CF are primarily aimed at preventing lung damage and lung function decline caused by bacterial infections. The role of Aspergillus infections is less understood, especially during childhood, and therefore evidence-based diagnostic and treatment guidelines are lacking. This narrative review summarizes our current understanding of the impact of Aspergillus on the airways of children and young people with CF.

Patients with allergic bronchopulmonary aspergillosis (ABPA) respond well to standard treatments (oral corticosteroids and/or antifungals); however, approximately in half of the patients, the condition recurs during tapering or early after treatment discontinuation. To avoid the adverse effects of long-term treatment, biologics targeting immunoglobulin E (IgE), eosinophils, or type 2 immune responses have been used in refractory ABPA. Omalizumab, an anti-IgE antibody, as well as mepolizumab and benralizumab targeting eosinophils has been consistently shown to decrease co-morbid asthma exacerbation and dose of oral corticosteroids. Furthermore, mepolizumab and benralizumab effectively improved chest radiographic abnormalities, such as mucus plugs in the bronchi. Data on dupilumab and tezepelumab are limited; however, they may be effective in patients who are resistant to treatment with omalizumab/mepolizumab/benralizumab. Future studies examining the effects of these biologics in preventing the recurrences/exacerbations of ABPA are warranted.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease that occurs due to a pulmonary immune system reaction to the antigens of Aspergillus Fumigatus. Central bronchiectasis, mucoid impaction, mosaic attenuation, centrilobular nodules, and tree-in-bud opacities are the most commonly observed CT scan findings of ABPA. Miliary molting is one of the rare radiological manifestations of ABPA. ABPA is usually seen in uncontrolled asthma and is very uncommon in patients without a prior history of asthma. We are reporting a case of ABPA that presented a miliary nodule in radiology and was never diagnosed as a case of asthma previously. Thus, in a patient with eosinophilia and miliary molting, ABPA is to be excluded. Early diagnosis and treatment can prevent end-stage fibrotic ABPA.

Allergic bronchopulmonary aspergillosis/mycosis (ABPA/ABPM) is characterized by increased serum levels of total and fungi-specific immunoglobulin E (IgE) and eosinophilic mucus plugs in the airways. Its classification as either an allergic or eosinophilic disease remains controversial. In the present review, we explored this topic based on three clinical studies that analyzed the clinical characteristics of ABPA/ABPM using a cluster analysis, factor analysis, and comparison between ABPM caused by Schizophyllum commune and ABPA. We also compared therapeutic responses to biologics targeting either IgE (omalizumab) or eosinophils (mepolizumab/benralizumab) to elucidate the role of these components in the pathogenesis of ABPA/ABPM. Based on these analyses, eosinophilic mucus plug formation in the airways is considered a cardinal feature of the development of ABPA/ABPM, whereas IgE responses to fungi are important factors that modulate disease manifestation.

Post-tuberculosis lung disease (PTLD) is a precursor to Aspergillus-related lung diseases. While Chronic Pulmonary Aspergillosis (CPA) has been extensively studied in the background of tuberculosis, Allergic Bronchopulmonary Aspergillosis (ABPA) has been reported sporadically with limited information on its prevalence, clinical-radiological features, and treatment outcomes.

This study, conducted in a high TB burden setting, aimed to address this knowledge gap by systematically evaluating ABPA in PTLD patients.

This retrospective cohort study screened PTLD patients presenting with respiratory or constitutional symptoms persisting for more than 3 months. The objective was to report the prevalence, clinical-radiological-laboratory data, and outcomes of ABPA-PTLD compared to a cohort of CPA (CPA-PTLD) and patients with PTLD (PTLD only).

Out of a total of 1012 PTLD patients, ABPA was seen in 2.27%, CPA in 20.75% and Aspergillus sensitization in 0.7%. ABPA patients primarily presented with breathlessness (91.3%) and cough (82.6%) while haemoptysis (43.5%), weight loss (13%), and anorexia (21.7%) were also observed, albeit less commonly than in CPA-PTLD. Bronchiectasis (100%) and nodules (87%) were more frequent in ABPA-PTLD patients, whereas consolidation (21.7%), cavities (30.4%), pleural thickening (8.7%), and 'fungal ball' (9.1%) were also seen, although less commonly than in CPA-PTLD. Most patients received azoles (78%) as first-line therapy, with symptomatic improvement (partial/complete) observed in ~78%.

ABPA may occur in PTLD patients, with specific clinical (e.g., haemoptysis) and radiological (e.g., cavity and fungal ball) features uncommon in other types of ABPA, but resembling other PTLD conditions. Future studies should focus on identifying differences in the natural course and appropriate treatment paradigms of ABPA-PTLD patients compared to ABPA occurring in asthma and cystic fibrosis patients.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease resulting from an overactive type 2 response to Aspergillus. Initial studies suggest that asthma biologics can effectively treat ABPA, but it is unclear which biologic class is superior.

We sought to compare the effectiveness of asthma biologics in the treatment of ABPA.

We performed a retrospective analysis of patients with ABPA treated with asthma biologics, and measured outcomes of respiratory exacerbations, daily oral corticosteroids, and antifungals. We assessed these variables while individuals were treated with 1 of 3 biologic classes: anti-IgE, anti-IL-5/IL-5 receptor alpha (IL-5Ra), anti-IL-4 receptor alpha (IL-4Ra).

A total of 21 patients were included in our analysis. Anti-IL-4Ra was associated with a significantly lower number of exacerbations and oral corticosteroid use compared with anti-IgE or anti-IL-5/IL-5Ra therapies. Anti-IL-4Ra also had significantly lower antifungal use than anti-IgE, and there was a trend toward lower antifungal use when compared with anti-IL-5/IL-5Ra. In a subgroup of 10 patients treated with 2 or more biologics sequentially, we found that 8 of them achieved clinical control on anti-IL-4Ra therapy after failing anti-IgE and/or anti-IL-5/IL-5Ra therapies.

Dupilumab blocks the IL-4Ra, resulting in the downstream inhibition of both IL-4 and IL-13 effector pathways. Dupilumab may benefit patients with ABPA by inhibiting the generation of airway mucus (IL-13), and by reducing local B-cell differentiation into IgE antibody-secreting cells (IL-4). On the basis of our findings and with the known molecular mechanisms of dupilumab, we believe that anti-IL-4Rα-targeted therapy may be more effective than anti-IgE or anti-IL-5/IL-5Rα therapies to treat ABPA.

Sensitization to Aspergillus, mucus plugs, and bacterial colonization may coexist and relate to a refractory phenotype during follow-up in asthma with bronchiectasis and allergic bronchopulmonary aspergillosis (ABPA).

This study aimed to clarify the features of Aspergillus-sensitized refractory asthma with bronchiectasis and determine the refractory phenotype in this population and ABPA.

This study included cases of the oldest available Aspergillus fumigatus-specific IgE data and chest computed tomography images from a nationwide survey of refractory asthma with bronchiectasis. The characteristics of the A fumigatus-IgE positive (Af sIgE+) group were investigated and compared with its nonsensitized counterpart (Af sIgE-) and ABPA group. Cluster analysis was conducted to determine the refractory phenotype.

The Af sIgE+ group (n = 35) demonstrated type 2 inflammation levels intermediate between the ABPA (n = 42) and Af sIgE- (n = 38) groups while exhibiting higher blood monocyte counts than the Af sIgE- group. Cluster analysis conducted in patients with ABPA and Af sIgE+ newly determined 2 clusters: one was characterized by a younger age of asthma onset with fungal detection in sputum, and the other was characterized by mucus plugs and inflammation with eosinophils and monocytes, which was significantly related to mucus plugs, airflow limitation, and trend to show exacerbation. In the latter cluster, mucus plugs persisted, and 30% yielded Pseudomonas aeruginosa in the sputum <5 years later.

The refractory phenotype with persistent mucus plugs was identified in Aspergillus-sensitized refractory asthma with bronchiectasis and ABPA. Mucus plug prevention is warranted.

We present a rare case of asymptomatic allergic bronchopulmonary aspergillosis (ABPA) concurrent with active pulmonary tuberculosis. Allergic bronchopulmonary aspergillosis is an immunological pulmonary disorder characterized by hypersensitivity to Aspergillus fumigatus, while pulmonary tuberculosis (PTB) is a complex infection caused by Mycobacterium tuberculosis (MTB). The association between pulmonary tuberculosis infections and Aspergillus infections remains a fascinating area of inquiry. A 26-year-old female patient exhibited no symptoms. However, her initial chest computed tomography revealed bronchiectasis with high-attenuation mucus plugs in the upper lobes, peripheral lung atelectasis, and a tree-in-bud pattern. To obtain a clear diagnosis, she visited multiple hospitals and incurred substantial time and financial costs. Active tuberculosis was initially confirmed using specialized detection methods, including metagenomic next-generation sequencing and Xpert MTB/RIF analysis of bronchoalveolar lavage fluid. Subsequent pathological biopsy and Aspergillus-specific antibody tests further confirmed the diagnosis of allergic bronchopulmonary aspergillosis combined with active tuberculosis. Following twelve months of antituberculosis therapy, an avoidable surgery, and three months of oral glucocorticoid treatment, the patient's lung lesions showed significant resolution. This case provides valuable insights into the clinical diagnosis and management of these two distinct infectious diseases.

There is limited data available about allergic bronchopulmonary aspergillosis (ABPA) in Pakistan. The aim of the study was to describe the radiological and microbiological profile of ABPA patients presenting to the outpatient pulmonary clinic of a tertiary care hospital in Karachi, Pakistan. A retrospective study was conducted on ABPA patients who presented to the pulmonary outpatient clinic at Aga Khan University Hospital, Karachi, Pakistan, from January 2017 to December 2019. Data was collected on microbiology and radiology features on a predesigned proforma. A total of 7759 asthmatic patients presented at the outpatient pulmonology clinic during the study period. Of the 245 patients labeled as ABPA, 167 fulfilled the inclusion criteria, and 91 (54.5%) were female (mean age 41.9±13.0 years). A high-resolution computed tomography scan of the chest was available for 126 patients. Of these, 104 (82.5%) patients had bronchiectasis. Central bronchiectasis was noted in 98 (94.2%) patients, mucus plugging in 71 (56.3%), and hyperinflation was seen in 30 (23.4%). Microbiological testing was available in 103/167 (61.7%) patients. The most common bacterial pathogen was Pseudomonas aeruginosa 32 (31.1%), followed by Hemophilus influenzae 16 (15.5%), and Moraxella catarrhalis 7 (9.7%). Aspergillus fumigatus 17 (23.6%) was the most common mold, followed by Aspergillus flavus 16 (22.2%) and Aspergillus niger 11 (15.3%). Co-infection (bacterial and fungal) was found in 18 (17.45%) patients. Bronchiectasis was frequently observed in our cohort of patients with ABPA. P. aeruginosa was found to be common among bacterial pathogens. Isolation of fungus is not uncommon in these patients.

Allergic bronchopulmonary aspergillosis/mycosis (ABPA/M) is a complex non-infectious pulmonary benign disease characterized by an immune response against aspergillus/fungus. Carcinoembryonic antigen (CEA), typically recognized as a tumor marker, also elevated in certain benign diseases. Few studies on ABPA/M cases presenting with elevated serum CEA levels have been reported.

A cohort of 115 patients diagnosed as ABPA/M were divided into two groups (CEA normal and CEA elevated). The characteristics of ABPA/M patients in terms of its demographic profile, clinical symptoms, pertinent clinical laboratory examinations were analyzed. Levels of cytokines (IL-4, IL-5, GM-CSF, IFN-γ) were analyzed by enzyme-linked immunosorbent assay. Comparative evaluation included pre-therapy and post-treatment eosinophil count and total IgE level, to evaluate therapeutic disparities between the two groups.

Among 115 cases of ABPA/M, 32 exhibited elevated serum CEA levels above baseline and 83 were normal. ABPA/M patients with elevated serum CEA tended to be younger (50, IQR [43-56] years vs 59, IQR [47-68] years; P < 0.05) with superior pulmonary function (FEV1/FVC ratio, 65.1% (44.2, 79.6) vs 79.1% (65.2, 84.2), P < 0.05), and showed marginally higher baseline levels of the total IgE (P < 0.05), blood eosinophils counts and ratios (P < 0.01) compared to those with normal CEA. Higher serum levels of IL-4, IL-5, GM-CSF and IFN-γ in ABPA/M patients with elevated serum CEA levels were observed (P < 0.0001). After treatment (at 12w), compared to ABPA/M patients with normal serum CEA, the decrease in eosinophil count and total IgE levels was less pronounced in ABPA/M patients with elevated serum CEA eosinophil count, 523±481.66 vs 267±200.68, P < 0.05; total IgE, 619±680.47 vs 263±400.90, P < 0.05), which indicates a poor response to treatment.

Monitoring serum CEA levels may serve as a supplementary tool in the clinical management of ABPA/M patients.

Staphylococcal enterotoxin and fungal sensitization can influence asthma severity; however, the effects on the clinical outcomes of asthma remain unclear. This study investigated the clinical outcomes of asthma in patients with or without staphylococcal enterotoxin sensitization and further analyzed the effects of fungal sensitization on the clinical outcomes of patients with staphylococcal enterotoxin sensitization.

This retrospective study included patients with asthma who had undergone a staphylococcal enterotoxin-specific immunoglobulin E test at our hospital between January and August 2021. Data on clinical manifestations, medication use, pulmonary function, clinic and emergency room visits and hospitalization were collected from 106 patients.

The prevalence of staphylococcal enterotoxin sensitization was 27.3%. Among the patients with staphylococcal enterotoxin sensitization, 50% also presented with fungal sensitization. The risk of hospitalization and emergency room visits was higher among patients with staphylococcal enterotoxin sensitization than among those without, as was the need for high-level asthma treatment, including triple inhaler therapy and biologics. After the 12-month Program enrollment, the rates of emergency room visits and hospitalization were similar in the two cohorts. Patients with concomitant staphylococcal enterotoxin and fungal sensitization exhibited a notable post-treatment decline in pulmonary function.

Adherence to asthma treatment protocols was shown to improve clinical outcomes in patients with or without staphylococcal enterotoxin sensitization. Among patients with staphylococcal enterotoxin sensitization, those with concomitant fungal sensitization were more likely to exhibit a rapid decline in pulmonary function during a 1-year high-level treatment program.

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.

Allergic bronchopulmonary aspergillosis (ABPA) is thought to occur more frequently in severe than in mild asthma. However, there are no precise data to support this hypothesis.

To determine the prevalence of ABPA in subjects with varying asthma severity.

We conducted a secondary analysis of prospectively collected data from 543 adult asthma subjects classified according to the 2004 Global Initiative for Asthma (GINA) guidelines. The asthma severity was categorized into mild, moderate, and severe. We report the prevalence of ABPA in each asthma category. We also performed multivariable logistic regression analysis to identify factors associated with ABPA in subjects with asthma.

We classified 81 (15%), 257 (47%), and 205 (38%) subjects as mild, moderate, and severe asthma. We diagnosed ABPA in 106 (19.5%) subjects. The prevalence of ABPA was 11.1% (9 of 81) in mild, 21% (54 of 257) in moderate, and 20.7% (43 of 205) in severe asthma (P = .12). Multivariable analysis identified age and asthma duration as significant factors associated with ABPA, whereas asthma severity was not significantly associated.

The prevalence of ABPA does not vary significantly with the severity of asthma. These findings support the revised International Society of Human and Animal Mycology (ISHAM) ABPA working group (AWG) recommendation for screening all asthma patients for ABPA, irrespective of asthma severity. Further large-scale studies across different geographic regions are warranted to validate these findings.

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.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease associated with significant morbidity. The ABPA Working Group (AWG) of the International Society for Human and Animal Mycology (ISHAM) revised their management guidelines in 2024, but there is currently no standardised tool to assess adherence to these recommendations.

We extracted key recommendations from the updated 2024 ISHAM-AWG guidelines, focusing on critical areas: screening and diagnosis of ABPA, managing acute and treatment-dependent ABPA, and monitoring treatment response. Each item was assigned a score ranging from zero to three. We assigned negative scores to interventions not recommended by the guidelines.

We identified 38 items indicative of optimal clinical care for patients with ABPA. The score for screening asthmatics for ABPA was set at three points. For diagnosing ABPA, 16 items were included, with a score ranging from 12 to 16 points, depending on the specific components used (predisposing conditions, serum A. fumigatus-specific IgE and IgG, serum total IgE, blood eosinophil count and chest computed tomography). The management of acute ABPA comprised 11 items, with a maximum score of three points. For treatment-dependent ABPA, there were nine items (scores ranging from -3 to 6). Follow-up care comprised 10 items with a maximum score of 10-13 points, covering imaging, spirometry, testing serum total IgE levels and therapeutic drug monitoring.

The EQUAL ABPA score has been developed as a comprehensive tool to quantify guideline adherence. Future studies will evaluate to which extent guideline adherence is associated with improved clinical outcomes for patients with ABPA.

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.

A female patient in her thirties presented with persistent cough and sputum, unresponsive to conventional treatments. Chest imaging showed infiltrative opacities and high attenuation mucus. On laboratory examination, eosinophil counts and immunoglobulin E were elevated. Cordyceps farinosa,a species of caterpillar fungi, was identified by bronchoscopy and subsequent DNA sequencing from the mucus plug. The symptoms improved after the removal of mucus plugs and cessation of exposure to the work environment. Allergic bronchopulmonary mycosis (ABPM) caused by C. farinosa has not been reported, and its pathogenicity is not well recognized. Herein, we report this case to understand the disease spectrum of ABPM and the pathogenicity of this rare fungi.

Eosinophilic extracellular traps (EETs) are reticular complexes comprising deoxyribonucleic-Acid (DNA) fibers and granule proteins.

EETs play a crucial role in antimicrobial host responses and are pathogenic when overproduced or under degraded. EETs created by eosinophils appear to enable vital immune responses against extra-cellular pathogens, nevertheless, trap overproduction is evident in pathology.

As considerably research is performed, new data affirmed that EETs can alter the outcome of respiratory ailment.

We probe into the disclosure and specificity of EETs produced in reaction to various stimuli and propose a role for those frameworks in ailment pathogenesis and the establishment of chronic, unresolved inflammation.

Whether EETs can be used as a prospective brand-new target for the diagnosis, treatment and prognosis of respiratory ailments is a scientific theme worth studying.

We probe into the disclosure and specificity of EETs produced in reaction to various stimuli and propose a role for those frameworks in ailment pathogenesis and the establishment of chronic, unresolved inflammation.

A 61-year-old woman, hospitalized for a persistent cough and dyspnea, had no history of bronchial asthma, but was undergoing chemotherapy for methotrexate-related lymphoproliferative disorder due to rheumatoid arthritis. Her peripheral blood eosinophil count was significantly increased, and chest CT revealed left lower lobe atelectasis and high-attenuation mucus. Bronchoscopy revealed mucous plugs and pathological examination revealed numerous eosinophils and filamentous fungi. Allergic bronchopulmonary mycosis (ABPM) caused by Scedosporium apiospermum was diagnosed using culture and genetic analyses. Treatment with corticosteroids and antifungal drugs led to improvement. ABPM caused by S. apiospermum is extremely rare, emphasizing the importance of species identification.

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.

Asthma is the most common chronic respiratory disease in childhood. Aspergillus fumigatus sensitivity may be involved in the pathogenesis of asthma by leading to different clinical presentations.

To investigate the demographic, clinical, laboratory, and radiological characteristics of A. fumigatus sensitivity in childhood asthma and identify associated risk factors and diagnostic parameters.

A total of 259 children with asthma were included in the study, 7 (2.7%) with allergic bronchopulmonary aspergillosis (ABPA), 84 (32.4%) with A. fumigatus-sensitized asthma (Af-SA), and 168 (64.9%) with A. fumigatus-unsensitized asthma (Af-UA).

Aspergillus sensitivity was associated with early asthma onset and longer asthma duration. Total IgE level and asthma severity are highest in ABPA and higher in Af-SA. Absolute eosinophil count was higher, and FEV1 was lower in Af-SA and ABPA. Aspergillus fumigatus was associated with greater odds of being male (odds ratio [OR], 2.45), having atopic dermatitis (OR, 3.159), Alternaria sensitivity (OR, 10.37), and longer asthma duration (OR, 1.266). The best cut-off values for detecting A. fumigatus positivity were 363.5 IU/mL for total IgE and 455 cells/μL for absolute eosinophil count. In Af-SA compared to Af-UA, centrilobular nodules and peribronchial thickening were more common, and the bronchoarterial ratio was higher.

Aspergillus sensitivity is a strong allergic stimulus in asthma, leading to laboratory, structural, clinical, and functional consequences. Af-SA is a distinct asthma endotype independent of ABPA that is characterized by increased risk of severe clinical presentations and impaired lung function.

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.

Numerous Aspergillus fumigatus (Af) airborne spores are inhaled daily by humans and animals due to their ubiquitous presence. The interaction between the spores and the respiratory epithelium, as well as its impact on the epithelial barrier function, remains largely unknown. The epithelial barrier protects the respiratory epithelium against viral infections. However, it can be compromised by environmental contaminants such as pollen, thereby increasing susceptibility to respiratory viral infections, including alphaherpesvirus equine herpesvirus type 1 (EHV-1). To determine whether Af spores disrupt the epithelial integrity and enhance susceptibility to viral infections, equine respiratory mucosal ex vivo explants were pretreated with Af spore diffusate, followed by EHV-1 inoculation. Spore proteases were characterized by zymography and identified using mass spectrometry-based proteomics. Proteases of the serine protease, metalloprotease, and aspartic protease groups were identified. Morphological analysis of hematoxylin-eosin (HE)-stained sections of the explants revealed that Af spores induced the desquamation of epithelial cells and a significant increase in intercellular space at high and low concentrations, respectively. The increase in intercellular space in the epithelium caused by Af spore proteases correlated with an increase in EHV-1 infection. Together, our findings demonstrate that Af spore proteases disrupt epithelial integrity, potentially leading to increased viral infection of the respiratory epithelium.