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Background 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. Method 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. Result 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). Conclusion 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.

Aspergillus fumigatus remains the most common species in all pulmonary syndromes, followed by Aspergillus flavus which is a common cause of allergic rhinosinusitis, postoperative aspergillosis and fungal keratitis. The manifestations of Aspergillus infections include invasive aspergillosis, chronic pulmonary aspergillosis and bronchitis. Allergic manifestations of inhaled Aspergillus include allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Triazoles are the mainstay of therapy against Aspergillus infections for treatment and prophylaxis. Lately, increased azole resistance in A. fumigatus has become a significant challenge in effective management of aspergillosis. Earlier studies have brought to light the contribution of non-cyp51 mutations along with alterations in cyp51A gene resulting in azole-resistant phenotypes of A. fumigatus. This review highlights the magnitude of azole-resistant aspergillosis and resistance mechanisms implicated in the development of azole-resistant A. fumigatus and address the therapeutic options available.

Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease caused by immunologic reactions initiated against Aspergillus fumigatus colonizing the airways of patients with asthma and cystic fibrosis. The common manifestations include treatment-resistant asthma, transient and fleeting pulmonary opacities and bronchiectasis. It is believed that globally there are about five million cases of ABPA, with India alone accounting for about 1.4 million cases. The occurrence of ABPA among asthmatic patients in special clinics may be as high as 13 per cent. Thus, a high degree of suspicion for ABPA should be entertained while treating a patient with bronchial asthma, particularly in specialized clinics. Early diagnosis and appropriate treatment can delay (or even prevent) the onset of bronchiectasis, which suggests that all patients of bronchial asthma should be screened for ABPA, especially in chest clinics. The current review summarizes the recent advances in the pathogenesis, diagnosis and management of ABPA.

The epidemiology of allergic bronchopulmonary aspergillosis (ABPA) in the United States is not well-described. To estimate national ABPA prevalence among patients with asthma or cystic fibrosis, characterize ABPA testing practices, and describe ABPA clinical features, treatment, and 6-month outcomes. We used the 2016–2022 Merative™ MarketScan® Commercial/Medicare and Multi-State Medicaid Databases to identify cohorts of patients with 1) asthma, 2) cystic fibrosis (CF), and 3) ABPA. We calculated ABPA prevalence per 10,000 patients with asthma or CF, assessed diagnostic testing for ABPA among patients with severe asthma, and described features of patients with ABPA using diagnosis and procedure codes. The overall ABPA prevalence among patients with asthma was 2.8/10,000 (Commercial/Medicare) and 1.0/10,000 (Medicaid). ABPA prevalence increased with asthma severity (Commercial/Medicare: mild 1.3, moderate 9.3, severe 70.6, Medicaid: mild 0.3, moderate 2.4, severe 32.4). Among patients with CF, ABPA prevalence was 183.7/10,000 (Commercial/Medicare) and 134.6/10,000 (Medicaid). Among patients with severe asthma, 10.3% (Commercial/Medicare) and 7.4% (Medicaid) received total immunoglobulin E testing, which is recommended for ABPA diagnosis. Among all patients with ABPA (Commercial/Medicare: n = 1,564, Medicaid: n = 410), ABPA treatments included inhaled corticosteroids (>70%), systemic corticosteroids (>62%), and antifungals (>18%). Patients with ABPA and Medicaid were more likely to experience hospitalization (45.1% vs. 22.5% of patients with Commercial/Medicare insurance) and respiratory failure (18.5% vs. 10.9%). This analysis provides initial estimates of national ABPA prevalence. Further studies could identify potential barriers to ABPA testing and investigate potential factors affecting payer-related differences in ABPA burden.

Allergic bronchopulmonary aspergillosis (ABPA) is characterized by an early allergic response and late-phase lung injury in response to repeated exposure to antigens, as a consequence of persistent fungal colonization of the airways. Here, we summarize the clinical and pathological features of ABPA, focusing on thick mucus plugging, a key observation in ABPA. Recent findings have indicated that luminal eosinophils undergo cytolytic extracellular trap cell death (ETosis) and release filamentous chromatin fibers (extracellular traps, ETs) by direct interaction with . Production of ETs is considered to be an innate immune response against non-phagocytable pathogens using a \"trap and kill\" mechanism, although eosinophil ETs do not promote damage or killing. Compared with neutrophils, eosinophil ETs are composed of stable and condensed chromatin fibers and thus might contribute to the higher viscosity of eosinophilic mucus. The major fate of massively accumulated eosinophils in the airways is ETosis, which potentially induces the release of toxic granule proteins and damage-associated molecular patterns, epithelial damage, and further decreases mucus clearance. This new perspective on ABPA as a luminal hypereosinophilic disease with ETosis/ETs could provide a better understanding of airway mucus plugging and contribute to future therapeutic strategies for this challenging disease.

Background 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. Methods 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. Results 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. Conclusion 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.

Background. Oral triazole therapy is well established for the treatment of invasive (IPA), allergic (ABPA), and chronic pulmonary (CPA) aspergillosis and is often long-term. Triazole resistance rates are rising internationally. Microbiological diagnosis of aspergillosis is limited by poor culture yield, leading to uncertainty about the frequency of triazole resistance. Methods. Using an ultrasensitive real-time polymerase chain reaction (PCR) assay for Aspergillus spp., we assessed respiratory fungal load in bronchoalveolar lavage (BAL) and sputum specimens. In a subset of PCR-positive, culture-negative samples, we further amplified the CYP51A gene to detect key single-nucleotide polymorphisms (SNPs) associated with triazole resistance. Results. Aspergillus DNA was detected in BAL from normal volunteers (4/11, 36.4%) and patients with culture or microscopy confirmed IPA (21/22, 95%). Aspergillus DNA was detected in sputum in 15 of 19 (78.9%) and 30 of 42 (71.4%) patients with ABPA and CPA, compared with 0% and 16.7% by culture, respectively. In culture-negative, PCR-positive samples, we detected triazole-resistance mutations (L98H with tandem repeat [TR] and M220) within the drug target CYP51A in 55.1% of samples. Six of 8 (75%) of those with ABPA and 12 of 24 (50%) with CPA had resistance markers present, some without prior triazole treatment, and in most despite adequate plasma drug concentrations around the time of sampling. Conclusions. The very low organism burdens of fungi causing infection have previously prevented direct culture and detection of antifungal resistance in clinical samples. These findings have major implications for the sustainability of triazoles for human antifungal therapy.

Allergic bronchopulmonary aspergillosis (ABPA) is a Th2 hypersensitivity lung disease in response to Aspergillus fumigatus that affects asthmatic and cystic fibrosis (CF) patients. Sensitization to A. fumigatus is common in both atopic asthmatic and CF patients, yet only 1-2% of asthmatic and 7-9% of CF patients develop ABPA. ABPA is characterized by wheezing and pulmonary infiltrates which may lead to pulmonary fibrosis and/or bronchiectasis. The inflammatory response is characterized by Th2 responses to Aspergillus allergens, increased serum IgE and eosinophilia. A number of genetic risks have recently been identified in the development of ABPA. These include HLA-DR and HLA-DQ, IL-4 receptor alpha chain (IL-4RA) polymorphisms, IL-10-1082GA promoter polymorphisms, surfactant protein A2 (SP-A2) polymorphisms, and cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations. The studies indicate that ABPA patients are genetically at risk to develop skewed and heightened Th2 responses to A. fumigatus antigens. These genetic risk studies and their consequences of elevated biologic markers may aid in identifying asthmatic and CF patients who are at risk to the development of ABPA. Furthermore, these studies suggest that immune modulation with medications such as anti-IgE, anti-IL-4 and/or IL-13 monoclonal antibodies may be helpful in the treatment of ABPA.

Aspergillus spp. can lead to allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitisation and Aspergillus bronchitis in CF. The relative frequencies of these entities have recently been ascertained in a large UK adult CF cohort. We have used this data to estimate the burden of aspergillosis and ABPA cases in adult CF patients in 30 countries reporting CF. National and international CF registry data was accessed and assessed for completeness and age distribution. Published proportions of ABPA (17.7%), Aspergillus sensitisation (14.6%) and Aspergillus bronchitis (30%) in CF were applied to those >18 years and compared with notified ABPA cases. Of the 76,201 estimated CF patients worldwide (not including India), 37,714 were >18 years. The proportion of adults to children varied from 63% in Norway to 20% in Brazil. ABPA caseload in adults is anticipated to be 6,675 cases of which only 2,221 cases (33%) are currently recorded, indicating substantial underdiagnosis. The ABPA diagnosis rate compared with estimated rates varies by country from 101% (France) to 14.5% (Greece), although genetic variation could account for genuine differences compared with the UK. Aspergillus bronchitis is not currently recognised or recorded in CF registries but there are an anticipated 10,988 adult cases. Aspergillus sensitisation, associated with increased bronchiectasis and reduced FEV1, affects an anticipated 5,506 patients without ABPA or Aspergillus bronchitis. Together ABPA and Aspergillus bronchitis are estimated to affect 17,989 adults, 47.7% of the adult CF population. ABPA also occurs in children and teenagers and 984 cases were documented in registries. Diagnosed ABPA rates by age were available for the ECFS registry, USA, UK, Ireland, Belgium and Netherlands. The rate was <1% under 4 years, and increased throughout childhood and adolescence, with marked variation between countries. Newly published diagnostic criteria and methods should facilitate better recognition of aspergillosis in CF, allowing better CF disease control.