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AbstractObjectiveMethodsResultsConclusionsThis study aimed to compare the clinical characteristics and treatment outcomes of allergic patients (AP) and non-allergic patients (NAP) with severe eosinophilic asthma (SEA) treated with anti-IL5/IL5R biologic agents (mepolizumab, benralizumab, or reslizumab) over one year. Sub-analyses assessed treatment response variations between AP and NAP based on the biological used and compared outcomes among AP with and without fungal allergy.Observational retrospective analysis. Clinical characteristics, laboratory findings, pulmonary function tests, Asthma Control Test (ACT) scores, oral corticosteroid (OCS) usage, and exacerbation frequency were assessed at the initiation of biological treatment and after one year.Sixty-five patients with SEA were included, 41 AP and 24 NAP. 55.4% were treated with mepolizumab, 33.8% with benralizumab, and 10.8% with reslizumab. Before anti-IL5/5R treatment, AP had worse baseline outcomes but there were no differences in pulmonary function. Mean annual exacerbation rate and percentage of patients requiring OCS and dose of prednisone were higher in AP than NAP. AP had significantly higher total IgE values. After one year of treatment, more AP discontinued OCS than NAP (p = 0.025). Both experienced a significant reduction in exacerbation frequency (p = 0.001) and improved respiratory function. 70.7% of AP and 60% of NAP improved ACT ≥3 points. There was no significant difference between AP and NAP using mepolizumab (p = 0.145) or benralizumab (p = 0.174) in reducing OCS.Anti-IL5/IL5R reduced the need for OCS and improved asthma control, regardless of allergic status. Fungal allergy led to lower ACT scores and higher exacerbations than other allergens; both groups improved with anti-IL5/ILR. [ABSTRACT FROM AUTHOR]

IntroductionThe aim of our work was to determine comprehensively the sensitization profile of patients hypersensitive to fungal allergenic components in the Ukrainian population, identifying features of their co-sensitization to allergens of other groups and establishing potential relationships between causative allergens and their ability to provoke this hypersensitivity.MethodsA set of programs was developed using Python and R programming languages, implementing the K-means++ clustering method. Bayesian networks were constructed based on the created clusters, allowing for the assessment of the probabilistic interplay of allergen molecules in the sensitization process of patients.Results and discussionIt was found that patients sensitive to fungi are polysensitized, with 84.77% of them having unique allergological profiles, comprising from 2 to several dozen allergens from different groups. The immune response to Alt a 1 may act as the primary trigger for sensitization to other allergens and may contribute to a high probability of developing sensitivity to grasses (primarily to Phl p 2), ragweed extract, and the Amb a 1 pectate lyase, as well as to pectate lyase Cry j 1 and cat allergen Fel d 1. Individuals polysensitized to molecular components of fungi were often sensitive to such cross-reactive molecules as lipocalins Fel d 4 and Can f 6, as well. Sensitivity to Ambrosia extract which dominated in the development of sensitization to ragweed pollen indicating the importance of different allergenic components of this plant's pollen. This hypothesis, along with the assumption that Phl p 2 may be the main trigger for sensitivity to grasses in patients with Alternaria allergy, requires further clinical investigation.

Background: Fungi are known for their ability to cause allergies, but data on individual sensitization to them are insufficient. The purpose of the study was to carry out a comprehensive analysis of the fungal allergens’ sensitization profile in the Ukrainian population and to determine both population and individual sensitivity to these allergens. Methods: We utilized a set of ALEX allergy test data from 20,033 inhabitants of 17 regions of Ukraine from 1 to 89 years conducted in 2020–2022. A complex of programs in the Python language was developed and Bayesian network analysis was applied to determine the sensitivity combinations in individual patients to various fungal components. Results: Sensitivity to Alt a 1 dominated and was observed in 79.39% of patients, and 62.17% of them were sensitive solely to Alt a 1. Exclusive sensitivity to Mala s 6 was second in individual patient profiles with a frequency of 4.06%. Combined sensitivity to Alt a 1 – Asp f 3 was third with a share of 3.28%. Pen ch and Cla h extracts stimulated the production of the lowest median sIgE levels. The highest median sIgE levels were for Alt a 1, Mala s 11 and Asp f 6, respectively. Median sIgE levels increased in adults compared to children for all components of Aspergillus fumigatus, as well as for Mala s 5 and Mala s 11. In the rest of the cases, they decreased in adults compared to children. The sensitization rates to fungi in general and specifically to Alternaria were lower in the western parts of Ukraine, especially in the Carpathian region, situated within the Broad-leaved Forest zone. The results of Bayesian modeling revealed that in the case of Alt a 1, the simultaneous absence of sensitivity to Cla h 8, Mala s 11, Mala s 5 and Mala s 6 molecules could condition the presence of sensitization to the major Alternaria allergen with a probability of 92.42%. In all other cases, there was a high probability of absence of sensitivity to particular allergen against the background of absence of sensitivity to other ones, which may indicate the independent development of sensitization to different fungal allergens. Conclusions: Sensitivity to Alt a 1 dominated in the studied population with a lower rate in the western regions. The highest median sIgE levels were induced by Alt a 1, Mala s 11 and Asp f 6. Bayesian Analysis suggest a high probability of the independent development of sensitization to different fungal allergens. The idea that sensitization to one allergen may be protective against sensitization to another one(s) requires further clinical study.

Introduction. Allergy to microscopic fungi (micromycetes), which can colonize the respiratory tract, is associated with an eosinophilic endotype of inflammation and severe disease course. Among the hallmarks of fungal allergy, experts identify fixed airways obstruction, bronchiectasis, and fibrosis. Currently, there has been proposed the term “allergic fungal airways disease” (AFAD), which combines various clinical phenotypes, which pathogenesis is based on IgE-mediated allergic reaction against fungal spores colonizing the respiratory tract. According to this approach, the AFAD group includes severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis (ABPA). A promising direction in AFAD treatment implies the use of genetically engineered biological drugs against T-2 inflammation. The aim of the study was to evaluate the prevalence ofAspergillusspp. sensitization and allergic bronchopulmonaryAspergillosis in patients with asthma. Materials and methods. A retrospective single-center registry study was conducted in the I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russian Federation. The study included 523 patients with asthma of varying severity. The level of total and specific blood serum IgE against aeroallergens, includingAspergillusspp., was analyzed by enzyme immunoassay. The diagnosis of asthma was established in accordance with the recommendations of the GINA working group and the Clinical recommendations of the Ministry of Health of the Russian Federation, fungal sensitization and ABPA — in accordance with the recommendations of the ISHAM working group.Results. During the examination of patients with asthma, sensitization toAspergillusspp. recorded in 16.6% cases, severe asthma with sensitization toAspergillusspp. — in 7.4%, ABPA — in 6.1%. In patients with allergic asthma, the prevalence of sensitization toAspergillusspp. was 22%, severe asthma with sensitization toAspergillusspp. — 10.1%, ABLA — 8.1%. Among patients with ABPA, females (64%) aged 40 years and older prevailed. The major clinical manifestations of ABPA were presented as cough (96%) and shortness of breath (76%), CT scan radiological changes were in a form of bronchiectasis (72%). Conclusion. A high prevalence of sensitization toAspergillusspp. in patients with asthma was found. It is necessary to includeAspergillusspp. into the list of tested allergens while examining patients with chronic lung diseases for timely detection of AFAD and prescription of proper anti-inflammatory or antimycotic therapy.

Background: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in Indian subjects with bronchial asthma. Methods: We searched the PubMed and Embase databases for studies from India reporting the prevalence of AS or ABPA in at least 50 asthmatics. The primary outcome of our study was to assess the prevalence of ABPA. The secondary outcomes were to evaluate the prevalence of AS in asthma and ABPA in Aspergillus-sensitized asthma. We pooled the prevalence estimates using a random effects model and examined the factors influencing the prevalence using multivariate meta-regression. Results: Of the 8,383 records retrieved, 34 studies with 14,580 asthmatics met the inclusion criteria. All the studies were from tertiary centers. The pooled prevalence of ABPA in asthmatics (26 studies; 5,554 asthmatics) was 16.2% [95% confidence interval (CI), 12.5-20.4]. The pooled prevalence of AS in asthma (29 studies; 13,405 asthmatics) was 30.9% (95% CI, 25.3-36.6), while the prevalence of ABPA in AS (20 studies; 1,493 asthmatics) was 48.2% (95% CI, 39.6-56.8). Meta-regression identified studies published after 2009 (OR 1.14; 95% CI, 1.02-1.28) and studies with severe asthmatics (OR 1.12; 95% CI, 1.00-1.26) as the only factors associated with higher ABPA prevalence. Conclusions: There is a high prevalence of ABPA in Indian asthmatic subjects at tertiary centers, underscoring the need for screening all asthmatic subjects in special asthma and chest clinics for ABPA. [ABSTRACT FROM AUTHOR]

Alternaria species are cosmopolitan fungi darkly pigmented by melanin that infect numerous plant species causing economically important agricultural spoilage of various food crops. Alternaria spp. also infect animals, being described as entomopathogenic fungi but also infecting warm-blooded animals, including humans. Their clinical importance in human health, as infection agents, lay in the growing number of immunocompromised patients. Moreover, Alternaria spp. are considered some of the most abundant and potent sources of airborne sensitizer allergens causing allergic respiratory diseases, as severe asthma. Among the numerous strategies deployed by Alternaria spp. to attack their hosts, the production of toxins, carrying critical concerns to public health as food contaminant, and the production of hydrolytic enzymes such as proteases, can be highlighted. Alternaria proteases also trigger allergic symptoms in individuals with fungal sensitization, acting as allergens and facilitating antigen access to the host subepithelium. Here, we review the current knowledge about the mechanisms of Alternaria pathogenesis in plants and animals, the strategies used by Alternaria to cope with the host defenses, and the involvement Alternaria allergens and mechanisms of sensitization. [ABSTRACT FROM AUTHOR]

Background: Fungal sensitization (FS) exacerbates asthma in patients who have elevated type 2 inflammatory response. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)‐4 and IL‐13, key and central drivers of type 2 inflammation in multiple diseases. Objective: This post hoc analysis, funded by the manufacturers of dupilumab, was conducted to assess dupilumab efficacy in patients from the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) and TRAVERSE open‐label extension (NCT02134028) study who had uncontrolled, moderate‐to‐severe asthma with type 2 inflammatory phenotype (defined as blood eosinophil count ≥150 cells/μL or FeNO ≥25 ppb) and with FS (defined as IgE specific to Alternaria alternata, Aspergillus fumigatus or Cladosporium herbarum >0.35 IU/mL). Methods: We evaluated annualized rate of severe exacerbations (AER), change from baseline in pre‐bronchodilator (BD) forced expiratory volume in 1 s (FEV1), asthma control (per 5‐item Asthma Control Questionnaire [ACQ‐5]) and biomarker levels (blood eosinophil count, fractional exhaled nitric oxide [FeNO], total IgE, fungal‐specific IgEs, thymus and activation‐regulated chemokine [TARC] and eotaxin‐3). Results: Dupilumab vs. placebo reduced AER, improved pre‐BD FEV1 and asthma control (ACQ‐5), and reduced serum IgE levels, blood eosinophil count, TARC, eotaxin‐3 and FeNO in patients both with and without FS after 52 weeks of treatment in QUEST. Reductions in asthma exacerbation rates and improvements in all other variables were sustained over the TRAVERSE open‐label extension study. Conclusion: Dupilumab demonstrated efficacy during prolonged treatment in patients with uncontrolled, moderate‐to‐severe asthma with FS. [ABSTRACT FROM AUTHOR]

Allergic bronchopulmonary aspergillosis (ABPA) is a lung disorder caused by immune‐mediated reactions mounted against Aspergillus fumigatus. The disorder most commonly complicates the course of patients with asthma and cystic fibrosis. From its first description in 1952, significant advances have been made in understanding the pathogenesis and the diagnosis and treatment of ABPA. In the last two decades, most research on ABPA has been published from India. The prevalence and clinical presentation may differ in India from that reported elsewhere. Herein, we review the epidemiology, clinical and radiological characteristics, and distinctive features of ABPA in the Indian subcontinent. To support the review, we surveyed pulmonologists nationwide to understand the challenges in diagnosing and managing ABPA. The survey has yielded valuable insights into the practices associated with the diagnosis and management of ABPA in India. [ABSTRACT FROM AUTHOR]

BACKGROUND: Various factors are involved in poorly controlled asthma despite adequate medication and proper inhalation techniques. Mold sensitivity has been associated with increased rates of hospital and intensive care admissions in adults. The fungal sensitization with severe asthma has been coined to describe fungal-sensitized patients with treatment-resistant asthma. The objective of this study was to compare asthma control between fungal- and nonfungal-sensitized (NFS) asthma patients. MATERIALS AND METHODS: Fifty-six cases of asthma were included over a period of 12 months in this prospective study. Data were captured using a proforma. Skin prick test was done as per standard protocol in all patients and a control assessment was done after 6–8 weeks of treatment as per GINA guidelines using Asthma Control Test (ACT) score. Data were analyzed using SPSS version 24.0. RESULTS: Out of 56 enrolled, 32.1% were fungal sensitized and 55.4% to NFS. Seven (12.5%) patients did not have clinically significant reactions. Maximum sensitization was found with Aspergillus spp. but no sensitization with Epicoccum and Cladosporium. Asthma was found to be poorly controlled in 77.8% of the fungal-sensitized group with a mean ACT score of 17.7 ± 1.8 as compared to 6.5% in the NFS group with mean ACT of 21.35 ± 1.6, respectively (P < 0.0001). CONCLUSION: Fungal sensitization was associated with poorly controlled asthma despite adequate medications and education. Early diagnosis and treatment in these patients with antifungals may improve quality of life, reduce exacerbations, and control of the primary disease.

Background. Many factors influence the development of atopic dermatitis (AD): genetic, environmental (including exposure to allergens), skin barrier damage, and activation of the T2-pathway immune response. Patients with AD, including those with severe disease, are prone to sensitization to various allergens, including fungal ones. Fungal sensitization (FS) promotes autoreactivity to the body's own structures due to shared epitopes with homologous fungal allergens. It can contribute to the development of allergic diseases, including AD, asthma, and rhinitis, as well as to their exacerbation and uncontrolled course. Since FS can be considered a factor aggravating AD, it is relevant to distinguish patients with FS and AD into a separate phenotype. Aim. To characterize the phenotype of patients with severe AD and FS using retrospective data analysis from a digital analytics platform in a real-world clinical setting. Materials and methods. A retrospective observational single-center study was conducted between 01.06.2017 and 01.07.2022. The study cohort included 88 patients with severe AD who were candidates for therapy or received treatment with either dupilumab or upadacitinib. FS was confirmed in 49 patients from the study group. Part of the cohort without FS (n=39) was used as a comparison group. Inclusion criteria: the age over 18 years old; severe AD (SCORAD40 points at the beginning of therapy); determination of specific immunoglobulin E to a panel of fungal allergens or individual fungi (or by the ImmunoCAP ISAC method to fungal allergen components). A digital analytics platform was used to generate primary data. Results. The phenotype of a patient with severe AD and confirmed FS was described. The patient profile is characterized by an extended sensitization spectrum (at least 34 allergen groups) with the most typical combination of pollen, epidermal, and FS. If there is a food allergy, it is of the classic "big eight" nature. Besides exacerbation of the skin disorder, its manifestations include angioedema of life-threatening localization and bronchospasm. Markers of T2 inflammation (high levels of immunoglobulin E and blood eosinophilia) are observed according to the test results, and the T2 endotype of allergy-related abnormalities is typical. Conclusion. Apparently, the presence of FS in patients with AD may exacerbate parenteral sensitization mechanisms, expanding its spectrum, including food allergens. Therefore, distinguishing the phenotype of severe AD with FS needs further detailing with a subsequent adaptation of monitoring and treatment methods of severe AD.

Background: The prevalence of aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) in asthmatic children remains unclear. Objective: To systematically review the literature to estimate the prevalence of AS and ABPA in children with bronchial asthma. Methods: We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in pediatric asthma. The primary outcome was to assess the prevalence of AS, while the secondary outcome was to evaluate the prevalence of ABPA. We pooled the prevalence estimates using a random effects model. We also calculated the heterogeneity and publication bias. Results: Of the 11,695 records retrieved, 16 studies with 2468 asthmatic children met the inclusion criteria. Most studies were published from tertiary centers. The pooled prevalence of AS in asthma (15 studies; 2361 subjects) was 16.1% (95% confidence intervals [CI], 9.3–24.3). The prevalence of AS was significantly higher in prospective studies, studies from India, and those from developing countries. The pooled prevalence of ABPA in asthma (5 studies; 505 children) was 9.9% (95% CI, 0.81–27.6). There was significant heterogeneity and publication bias for both outcomes. Conclusions: We found a high prevalence of AS and ABPA in asthmatic children. There is a need for community-based studies from different ethnicities using a standard methodology to ascertain the true prevalence of AS and ABPA in pediatric asthma. [ABSTRACT FROM AUTHOR]

Background: Airway allergies such as asthma and allergic rhinitis, as well as their comorbidities, are increasing worldwide, causing significant socioeconomic health burdens to societies. It is estimated that between 3% and 10% of the population is allergic to fungi. The type of fungal sensitization varies from one geographical region to another. The present study aimed to identify the common fungal aeroallergen sensitization patterns among airway-allergic patients residing in the Zagazig locality, Egypt, in order to obtain a better understanding of fungal allergy, in addition to improving the awareness and management strategies for those patients. Methods: The present cross-sectional study included 200 allergic rhinitis and asthma patients. Sensitization to fungal aeroallergens was evaluated by skin prick testing and in vitro measurement of total and specific immunoglobulin E. Results. As determined by a skin prick test, 58% of the patients studied were allergic to mixed molds. Alternaria alternata was the predominant fungal aeroallergen among the studied patients (72.2%), which was followed by Aspergillus fumigatus (53.45%), Penicillium notatum (52.6%), Candida albicans (34.5%), and Aspergillus niger (25%). Conclusion: Mixed mold sensitization ranked fourth among the most frequent aeroallergens in airway-allergic patients, and Alternaria alternata was the most frequently encountered fungal aeroallergen in the Zagazig locality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Various factors are involved in poorly controlled asthma despite adequate medication and proper inhalation techniques. Mold sensitivity has been associated with increased rates of hospital and intensive care admissions in adults. The fungal sensitization with severe asthma has been coined to describe fungal-sensitized patients with treatment-resistant asthma. The objective of this study was to compare asthma control between fungal- and nonfungal-sensitized (NFS) asthma patients. MATERIALS AND METHODS: Fifty-six cases of asthma were included over a period of 12 months in this prospective study. Data were captured using a proforma. Skin prick test was done as per standard protocol in all patients and a control assessment was done after 6–8 weeks of treatment as per GINA guidelines using Asthma Control Test (ACT) score. Data were analyzed using SPSS version 24.0. RESULTS: Out of 56 enrolled, 32.1% were fungal sensitized and 55.4% to NFS. Seven (12.5%) patients did not have clinically significant reactions. Maximum sensitization was found with Aspergillus spp. but no sensitization with Epicoccum and Cladosporium. Asthma was found to be poorly controlled in 77.8% of the fungal-sensitized group with a mean ACT score of 17.7 ± 1.8 as compared to 6.5% in the NFS group with mean ACT of 21.35 ± 1.6, respectively (P < 0.0001). CONCLUSION: Fungal sensitization was associated with poorly controlled asthma despite adequate medications and education. Early diagnosis and treatment in these patients with antifungals may improve quality of life, reduce exacerbations, and control of the primary disease. [ABSTRACT FROM AUTHOR]

Background. Fungal sensitization (FS) often escapes the attention of clinicians when assessing the spectrum of sensitization in patients with atopic diseases. According to cohort studies is found in 310% of the general population and in 720% of asthmatics; the proportion of patients with severe bronchial asthma (SBA) with HS ranges from 35 to 75%. Fungal conidia have a 1000-fold higher exposure and are among the most important clinically relevant allergens in asthma. Exposure to fungal allergens is capable of generating a sustained T2 response with production of proinflammatory cytokines such as IL-5 and 13, which is indirectly related to the severity of airway eosinophilia. The identification of specific serum IgE is considered the benchmark diagnostic sign of FS, and the encapsulated hydrophobic carrier polymer system is considered preferable to skin prick tests. The process of reclassifying diseases with fungal lung lesions is confusing treatment strategies, leaving the FS problem underestimated. A series of publications have shown that omalizumab and other biologics targeting IL-5 or IL-5 receptor (IL5R) alpha are effective in treating SBA with FS. However, there remains an unmet need in real clinical practice for standardized approaches to genetically engineered biological therapies (BT) for different phenotypes of SBA, especially those associated with impaired microbiological homeostasis and this type of sensitization. Aim. Using retrospective analysis of clinical-dynamic observational data from patients on BT treatment in a real clinical setting to determine phenotypic features of severe allergic bronchial asthma with FS and to perform additional detailed analysis of a cohort of patients on anti-IgE therapy. Materials and methods. A retrospective observational single-center registry study was conducted between June 2017 and August 2021 at the City Reference Center for Allergology and Immunology. The baseline cohort consisted of 198 patients with severe allergic AD who were in the initial phase of BT. Inclusion criteria: age of patients over 18 years; presence of severe allergic bronchial asthma. Complex initial examination of patients included determination of FS by two methods: ImmunoCap ISAC to fungal allergic components alt a1, alt 6 (fungi of genus Alternaria) and asp f1, asp f3, asp f6 (fungi of genus Aspergillus). Specific IgE determinations on fungal panels. Sensitization to fungi was detected in 47 people during allergy examination. The following criteria were considered in evaluation of response to omalizumab: AST score less than 19 and/or difference between initial AST score and this score in dynamics less than 3 points; FEV 1 score less than 80; combination of 2 listed criteria. The minimum period of BT was 16 weeks. Nonparametric methods of descriptive statistics were used: median, interquartile range. Differences were considered significant at p0.05. Data were statistically processed using nonparametric methods in IBM SPSS Statistics V-22 program. MannWhitney U-test and KruskalWallis one-way analysis of variance were used to compare quantitative characteristics. Fisher's 2 test was used to compare qualitative characteristics. Results. Characteristics of the eosinophilic phenotype of SBA combined with FS: middle-aged patients, more often women, with relatively early onset of AD and high baseline eosinophil levels before prescription of biological drug therapy. Concomitant atopic dermatitis and food allergies are additional frequent features of this phenotype. Analysis of the effect of FS on achieving response to omalizumab and further consideration of switching to alternative therapy in SBA and FS patients showed the need to avoid premature revision and perform no earlier than the 10th month of therapy due to delayed response formation. Given the aggressive impact of FS on the barrier functions of the bronchial tree epithelium, it is advisable to test patients for FS at the initial diagnosis of AD. In the presence of atopic dermatitis and/or food allergy as T2 comorbidities in patients with SBA, early testing for FS and increased control of local and systemic inflammation are appropriate, which may improve long-term outcomes and reduce risks of further damage to natural barriers. Conclusion. Further research on various aspects of FS and its role in allergic diseases is extremely relevant in the current context.

Background: The diagnostic accuracy of immunoassays versus immunoprecipitation methods for detecting A.fumigatus‐specific IgG in patients with allergic bronchopulmonary aspergillosis (ABPA) complicating asthma remains unclear. Methods: We performed a systematic review to identify studies describing both the methods in the same ABPA subjects. We assessed study quality using the QUADAS‐2 tool. We derived the relative sensitivity and specificity using the HSROC meta‐regression model. We calculated the number‐needed‐to‐test using an immunoassay to detect one additional positive test in ABPA. Results: Our search yielded 20 studies (796 ABPA and 929 controls). The studies had a high risk of bias. The summary estimates for sensitivity and specificity of immunoprecipitation methods were 68.6% (95% CI, 48.4–83.5) and 93.8% (95% CI, 83.6–97.8), respectively, while for immunoassays they were 85.2% (95% CI, 73.3–92.3) and 84.6% (95% CI, 76.0–90.5), respectively. The relative sensitivity and specificity of immunoassays compared to immunoprecipitation tests were 1.29 (95% CI, 1.1–1.6) and 0.91 (95% CI, 0.85–0.97), respectively. The automated immunoassays (1.77; 95% CI, 1.1–2.8) had better relative sensitivity than the manual (1.1; 95% CI, 1.02–1.18) assays compared to immunoprecipitation. The relative specificity of manual immunoassays (0.95; 95% CI, 0.91–0.99) was significantly lower, while that of automated (0.88; 95% CI, 0.77–1.0) assays was lower but not statistically different. One additional positive result was detected for every six (95% CI, 5–7) tests performed with immunoassay (versus immunoprecipitation). Conclusion: Compared to immunoprecipiation methods, automated immunoassays have higher sensitivity and similar specificity, manual immunoassays have higher sensitivity and lower specificity, while automated immunoassays have higher sensitivity and similar specificity for detecting A.fumigatus‐IgG in patients with ABPA. [www.crd.york.ac.uk/prospero/display_record.php?RecordID=309864]. [ABSTRACT FROM AUTHOR]

Sensitization to fungal allergens is one of the proposed phenotypes in asthma. An association between fungal sensitization and worse clinical outcomes is apparent. Moreover, fungal sensitization in asthma that is associated with different type of immunological mechanism has been reported. How the role of cytokines mediates the association between fungal sensitization and poorer asthmatic outcomes remains unclear. We aimed to determine role of cytokines in the relationship between fungal sensitization and worse clinical outcomes in asthma. Method: We conducted a prospective study to recruit adult patients with asthma. Data including age, sex, height, weight, smoking history, medication, emergency visit and admission, pulmonary function testing result, and Asthma Control Test (ACT) scores were collected. We used the automated BioIC method to measure fungal allergen sIgE in sera. Serum levels of Interleukin (IL) -4, IL-13, IL-6, IL-9, IL-10, IL-17 A, IL-22, Interferon (IFN) -γ, Immunoglobulin E (IgE), Tumor necrosis factor-α (TNF-α), and Transforming growth factor-β (TGF-β) were measured using ELISA. Result: IL-6 and IL-17A had a significant positive correlation between sensitization and most fungi species compared to IgE. Sensitization to Candida albicans had strongly positive association both with IL-6 and IL-17A. However, only IL-17A had significant relationship with ED visit times. The mediation analysis result indicates that IL-17A had a significant positively mediating effect (ME) on the association between Candida albicans and ED visit times. Conclusion: IL-17A is a potential mediator to link Candida albicans sensitization and ED visits for asthma. We suggest that patients with fungal sensitization, such as Candida albicans, have poorer outcomes associated with Th17-mediated immune response rather than Th2. [ABSTRACT FROM AUTHOR]

Background: The modified International Society for Human and Animal Mycology (ISHAM) allergic bronchopulmonary aspergillosis (ABPA) working group (AWG) criteria lists up to five components for diagnosing ABPA in asthmatics. Whether eliminating specific components of the existing criteria would have the same diagnostic utility as the original remains unknown. Objective: To evaluate the performance of several simplified criteria for diagnosing ABPA. Methods: We compared the performance of seven new criteria (after excluding or modifying one or more of the components of the ISHAM-AWG criteria) with the modified ISHAM-AWG criteria in asthmatic subjects using latent class analysis (LCA). We also tested the performance of the newer criteria using accuracy measures against a multidisciplinary team (MDT) diagnosis of ABPA. We considered the diagnostic accuracy of the newer criteria to be acceptable if the correct classification and false-negative rates were >95% and <5%, respectively, on an MDT evaluation. Results: We analyzed data from 543 asthmatic subjects (58.8% women; mean age, 36.8 years). Using LCA, the sensitivity of the A.fumigatus-specific IgE-based criteria ranged from 92-99%, while the specificity varied between 92% and 100%. The MDT diagnosed ABPA in 106 (19.5%) subjects. Using MDT as the reference standard, the correct classification and false-negative rates were >95% for three of the seven and <5% for four of the seven newer criteria. Conclusions: We found several of the newly developed criteria to perform, like the modified ISHAM-AWG criteria, for diagnosing ABPA complicating asthma. A prospective study in current clinical algorithms is required for validating our observations. [ABSTRACT FROM AUTHOR]

Objective: to analyze dynamics of sporulation of mold fungi in order to predict the risks of exacerbation of allergic diseases in Samara.Materials and methods. We evaluated the concentration of fungal spores between April 1st and September 30th in 2016–2019 in the air. Mold spores were captured using an impactor trap on slides covered with a mixture of vaseline and wax with subsequent counting of spore number and their identification.Results. The mean vegetative period of mold fungi in Samara city was 164 days. We have identified spores of Cladosporium and Alternaria, which accounted for 34.4 % of the total number of spores in the atmospheric air of Samara. Cladosporium spores were detected during the entire observation period; their proportion was 15.3% from the total number of fungal spores, their maximum concentrations were within the normal limits and did not exceed 960 spores/m3. The proportion of Alternaria spores was 19.1%. In some periods, concentrations of Alternaria spores exceeded threshold values: the concentration between 10 and 100 spores/m3 was observed 4 to 31 days per months; the concentration above 100 spores/m3 was observed 2 to 25 days per month. The highest total monthly concentration of Alternaria spores was detected in July–September, during the period of sagebrush and ragweed pollination, which can potentially hamper the diagnosis and treatment of patients who have exacerbations of their allergic diseases in this period.Conclusion. We have identified the main taxa of mold fungi, analyzed their regional specificity and assessed the risk of allergic diseases in individuals sensitized to Alternaria and Cladosporium species. Our findings will help to optimize the diagnosis, treatment, and prevention of allergic diseases in the region.

Chun-Yu Lin,1,2 Yu-Chen Huang,1,2 Hung-Yu Huang,1,2 Fu-Tsai Chung,1,2 Yu-Lun Lo,1,2 Shu-Min Lin,1,2 Chun-Hua Wang,1,2 Han-Pin Kuo3 1Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3College of Medicine, Taipei Medical University, Taipei, TaiwanCorrespondence: Chun-Hua WangDepartment of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kweishan, Taoyuan 33305, TaiwanTel +8863-3281200 ext.8467Fax +8863-3287787Email wchunhua@ms7.hinet.netBackground: The efficacy of antifungal therapy in fungal-associated severe asthma remains controversial.Objective: We aimed to evaluate the differences in the clinical presentation and response to antifungal therapy between severe asthmatics with fungal sensitization and positive fungal isolates.Methods: This retrospective study included 73 patients with severe asthma from January 2004 to December 2017. We examined the presentation, medication, exacerbations, pulmonary function, serum IgE, blood eosinophils, and sputum culture results. Follow-up care was provided to each patient for minimum 3 years.Results: We classified the patients into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n=16); group 2, positive fungal sensitization (n=16); group 3, positive fungal isolates (n=31); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n=10). There were four participants in group 2, 15 in group 3, and 6 in group 4 had received itraconazole therapy for 3 months. Patients in group 3 presented with lower serum IgE level than those in groups 2 and 4. Antifungal therapy significantly improved ACT score during the first year in groups 3 (from 18 [15– 22] to 24 [23– 24], p=0.0004) and resulted in a long-lasting ACT improvement till the third year in group 3 (from 18 [15– 22] to 24 [22– 24], p=0.0013).Conclusion: Antifungal therapy could effectively control the symptoms in patients with severe asthma with positive fungal isolates, contrary to those with merely fungal sensitization; therefore, highlighting the need for a more precise treatment strategy in future for fungal-associated severe asthma.Keywords: fungal-associated asthma, severe asthma, fungal sensitization, antifungal therapy, itraconazole

BackgroundThe modified International Society for Human and Animal Mycology (ISHAM) allergic bronchopulmonary aspergillosis (ABPA) working group (AWG) criteria lists up to five components for diagnosing ABPA in asthmatics. Whether eliminating specific components of the existing criteria would have the same diagnostic utility as the original remains unknown.ObjectiveTo evaluate the performance of several simplified criteria for diagnosing ABPA.MethodsWe compared the performance of seven new criteria (after excluding or modifying one or more of the components of the ISHAM-AWG criteria) with the modified ISHAM-AWG criteria in asthmatic subjects using latent class analysis (LCA). We also tested the performance of the newer criteria using accuracy measures against a multidisciplinary team (MDT) diagnosis of ABPA. We considered the diagnostic accuracy of the newer criteria to be acceptable if the correct classification and false-negative rates were >95% and 95% for three of the seven and

Background: The prevalence of aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) in asthmatic children remains unclear. Objective: To systematically review the literature to estimate the prevalence of AS and ABPA in children with bronchial asthma. Methods: We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in pediatric asthma. The primary outcome was to assess the prevalence of AS, while the secondary outcome was to evaluate the prevalence of ABPA. We pooled the prevalence estimates using a random effects model. We also calculated the heterogeneity and publication bias. Results: Of the 11,695 records retrieved, 16 studies with 2468 asthmatic children met the inclusion criteria. Most studies were published from tertiary centers. The pooled prevalence of AS in asthma (15 studies; 2361 subjects) was 16.1% (95% confidence intervals [CI], 9.3–24.3). The prevalence of AS was significantly higher in prospective studies, studies from India, and those from developing countries. The pooled prevalence of ABPA in asthma (5 studies; 505 children) was 9.9% (95% CI, 0.81–27.6). There was significant heterogeneity and publication bias for both outcomes. Conclusions: We found a high prevalence of AS and ABPA in asthmatic children. There is a need for community-based studies from different ethnicities using a standard methodology to ascertain the true prevalence of AS and ABPA in pediatric asthma.

Background: Airway allergies such as asthma and allergic rhinitis, as well as their comorbidities, are increasing worldwide, causing significant socioeconomic health burdens to societies. It is estimated that between 3% and 10% of the population is allergic to fungi. The type of fungal sensitization varies from one geographical region to another. The present study aimed to identify the common fungal aeroallergen sensitization patterns among airway-allergic patients residing in the Zagazig locality, Egypt, in order to obtain a better understanding of fungal allergy, in addition to improving the awareness and management strategies for those patients. Methods: The present cross-sectional study included 200 allergic rhinitis and asthma patients. Sensitization to fungal aeroallergens was evaluated by skin prick testing and in vitro measurement of total and specific immunoglobulin E. Results. As determined by a skin prick test, 58% of the patients studied were allergic to mixed molds. Alternaria alternata was the predominant fungal aeroallergen among the studied patients (72.2%), which was followed by Aspergillus fumigatus (53.45%), Penicillium notatum (52.6%), Candida albicans (34.5%), and Aspergillus niger (25%). Conclusion: Mixed mold sensitization ranked fourth among the most frequent aeroallergens in airway-allergic patients, and Alternaria alternata was the most frequently encountered fungal aeroallergen in the Zagazig locality.

Introduction: The aim of our work was to determine comprehensively the sensitization profile of patients hypersensitive to fungal allergenic components in the Ukrainian population, identifying features of their co-sensitization to allergens of other groups and establishing potential relationships between causative allergens and their ability to provoke this hypersensitivity., Methods: A set of programs was developed using Python and R programming languages, implementing the K-means++ clustering method. Bayesian networks were constructed based on the created clusters, allowing for the assessment of the probabilistic interplay of allergen molecules in the sensitization process of patients., Results and Discussion: It was found that patients sensitive to fungi are polysensitized, with 84.77% of them having unique allergological profiles, comprising from 2 to several dozen allergens from different groups. The immune response to Alt a 1 may act as the primary trigger for sensitization to other allergens and may contribute to a high probability of developing sensitivity to grasses (primarily to Phl p 2), ragweed extract, and the Amb a 1 pectate lyase, as well as to pectate lyase Cry j 1 and cat allergen Fel d 1. Individuals polysensitized to molecular components of fungi were often sensitive to such cross-reactive molecules as lipocalins Fel d 4 and Can f 6, as well. Sensitivity to Ambrosia extract which dominated in the development of sensitization to ragweed pollen indicating the importance of different allergenic components of this plant's pollen. This hypothesis, along with the assumption that Phl p 2 may be the main trigger for sensitivity to grasses in patients with Alternaria allergy, requires further clinical investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor HR declared a past co-authorship with the author VK., (© 2024 Kalyniuk, Rodinkova, Yuriev, Mokin, Losenko, Kryvopustova, Zabolotna and Gogunska.)

Background. To evaluate the prevalence and clinical outcomes caused by combined pollen and fungal sensitization in Samara region. Materials and methods. The general and allergological observation of patients with symptoms of allergic rhinitis (AR) and bronchial asthma was performed: detection of specific IgE level to fungal extracts and other respiratory allergens (RIDA Allergyscreen, R-Biopharm, Germany), and to Alt a 1, Art v 1, Amb a 1 molecules (Phadia 250 ImmunoCap ISAC). Results. Patients were diagnosed with hypersensitivity to various groups of allergens, including fungal and pollen allergens. Sensitization to Alternaria predominated among patients allergic to fungi. Combined fungal and pollen sensitization was found among 13% adults and 17% children. Sensitization to Alternaria is a risk factor of asthma in childhood. Detection of specific IgE to Alt a 1 confirmed true sensitization in 60%; sensitization to Alt a 1 was found in 10% of patients with true artemisia and ambrosia sensitization. Data obtained coordinate with results of regional aeropolinologic monitoring, which confirms the high significance of genera Alternaria and weed pollen in provoking respiratory allergy in Samara, especially during the period from the 3rd decade of July, which is characterized by pick concentration level of these allergens in the air and exacerbation of allergic rhinitis and asthma in sensitive patients. Conclusion. The existence of combined fungal and pollen sensitization influence the clinical outcomes and propose application of personalized treatment methods.

Background and Purpose: Itraconazole therapy has been reported to control asthma in severe therapy-resistant asthma with fungal sensitization. The aim of this study was to investigate the impact of anti-fungal therapy on the treatment of severe asthma, irrespective of sensitization. Materials and Methods: This active comparator clinical trial was performed on 110 therapy-resistant asthmatic patients who were randomly assigned into two groups of case and control. The patients in the case group were administered 200 mg itraconazole twice a day and the control group received 10 mg prednisolone after breakfast for 4 months. The asthma control test (ACT) which was used as a marker for the global evaluation of treatment effectiveness (GETE) was applied as the primary endpoint parameter. Cough, dyspnea, and sleep disturbance were measured on a scale of 1-4, with 1 representing no symptom and 4 indicating severe exhausting disturbance. Results: Based on the obtained results, 71% of the itraconazole group demonstrated a marked improvement in the GETE score after a four-month treatment. Itraconazole was able to suppress clinical symptoms, including cough, dyspnea, and night symptoms, and their physical exam was indicative of normalization in 60% of the patients. On the other hand, the patients in the parallel group "prednisolone" were only able to control dyspnea. The ACT score represented a notable improvement with itraconazole (mean: 14 before the trial and >20 after the trial) and spirometry parameters underwent a considerable change from obstructive pattern to normal. Furthermore, adverse effects were only detected in 6% of itraconazole users. Conclusion: The results of this clinical trial indicted the effectiveness of antifungal therapy for the control of the clinical condition of a subgroup of patients with severe steroid-refractory asthma.

Aspergillus fumigatus colonization in the patients with cystic fibrosis (CF) may cause sensitization against A. fumigatus and/or allergic bronchopulmonary aspergillosis (ABPA), which significantly worsens the course of underlying disease. At the present time, new diagnostic tests are searched for detection of fungal sensitization in these patients. The aim of this work was to evaluate an opportunity of application of basophile activation test with A. fumigatus allergen in vitro using flow cytometry, aiming for identification of fungal sensitization in the CF patients. The study included 190 patients with CF aged 1 to 37 years. All the patients underwent common allergy screening (skin tests with fungal allergens, determination of serum levels of total IgE and specific IgE for the fungal allergens), and mycological examination (microscopy and culture of respiratory substrates). Computed tomography of the chest was performed upon clinical indications. The basophil activation test with the A. fumigatus allergen was performed in 10 CF patients with ABPA, and 10 CF patients without ABPA, in addition to the standard allergological examination. Frequency of sensitization to A. fumigatus in the patients with cystic fibrosis was 27%, the incidence of allergic bronchopulmonary aspergillosis was 5.7%. The number of eosinophils, total IgE and specific IgE levels in CF patients with ABPA were significantly higher than in CF patients without ABPA. In blood of the ABPA patients we have identified 68.5 (52.5-81.5%) of basophilic leukocytes activated by A. fumigatus allergen, with a stimulation index of 17.07 (10.30-27.70). In appropriate comparison group, the stimulation index did not exceed 1.5 (p = 0.000). Direct positive correlation between the levels of specific IgE to A. fumigatus and the number of basophils activated by A. fumigatus allergens was revealed (r = 0.77; р < 0.05). FVC values and the body mass index in CF patients with ABPA were significantly lower when compared with the patients without fungal sensitization. Introduction of the basophil activation test, along with standard techniques, may enable a more differentiated assessment of ABPA development in CF patients. Timely detection of associations between A. fumigatus sensitization and clinical status of CF patients will facilitate early and effective administration of specific therapy.

Sensitization to fungal allergens is one of the proposed phenotypes in asthma. An association between fungal sensitization and worse clinical outcomes is apparent. Moreover, fungal sensitization in asthma that is associated with different type of immunological mechanism has been reported. How the role of cytokines mediates the association between fungal sensitization and poorer asthmatic outcomes remains unclear. We aimed to determine role of cytokines in the relationship between fungal sensitization and worse clinical outcomes in asthma. Method: We conducted a prospective study to recruit adult patients with asthma. Data including age, sex, height, weight, smoking history, medication, emergency visit and admission, pulmonary function testing result, and Asthma Control Test (ACT) scores were collected. We used the automated BioIC method to measure fungal allergen sIgE in sera. Serum levels of Interleukin (IL) -4, IL-13, IL-6, IL-9, IL-10, IL-17 A, IL-22, Interferon (IFN) -γ, Immunoglobulin E (IgE), Tumor necrosis factor-α (TNF-α), and Transforming growth factor-β (TGF-β) were measured using ELISA. Result: IL-6 and IL-17A had a significant positive correlation between sensitization and most fungi species compared to IgE. Sensitization to Candida albicans had strongly positive association both with IL-6 and IL-17A. However, only IL-17A had significant relationship with ED visit times. The mediation analysis result indicates that IL-17A had a significant positively mediating effect (ME) on the association between Candida albicans and ED visit times. Conclusion: IL-17A is a potential mediator to link Candida albicans sensitization and ED visits for asthma. We suggest that patients with fungal sensitization, such as Candida albicans, have poorer outcomes associated with Th17-mediated immune response rather than Th2.

Background: Fungi are known for their ability to cause allergies, but data on individual sensitization to them are insufficient. The purpose of the study was to carry out a comprehensive analysis of the fungal allergens' sensitization profile in the Ukrainian population and to determine both population and individual sensitivity to these allergens., Methods: We utilized a set of ALEX allergy test data from 20,033 inhabitants of 17 regions of Ukraine from 1 to 89 years conducted in 2020-2022. A complex of programs in the Python language was developed and Bayesian network analysis was applied to determine the sensitivity combinations in individual patients to various fungal components., Results: Sensitivity to Alt a 1 dominated and was observed in 79.39% of patients, and 62.17% of them were sensitive solely to Alt a 1. Exclusive sensitivity to Mala s 6 was second in individual patient profiles with a frequency of 4.06%. Combined sensitivity to Alt a 1 - Asp f 3 was third with a share of 3.28%. Pen ch and Cla h extracts stimulated the production of the lowest median sIgE levels. The highest median sIgE levels were for Alt a 1, Mala s 11 and Asp f 6, respectively. Median sIgE levels increased in adults compared to children for all components of Aspergillus fumigatus , as well as for Mala s 5 and Mala s 11. In the rest of the cases, they decreased in adults compared to children. The sensitization rates to fungi in general and specifically to Alternaria were lower in the western parts of Ukraine, especially in the Carpathian region, situated within the Broad-leaved Forest zone. The results of Bayesian modeling revealed that in the case of Alt a 1, the simultaneous absence of sensitivity to Cla h 8, Mala s 11, Mala s 5 and Mala s 6 molecules could condition the presence of sensitization to the major Alternaria allergen with a probability of 92.42%. In all other cases, there was a high probability of absence of sensitivity to particular allergen against the background of absence of sensitivity to other ones, which may indicate the independent development of sensitization to different fungal allergens., Conclusions: Sensitivity to Alt a 1 dominated in the studied population with a lower rate in the western regions. The highest median sIgE levels were induced by Alt a 1, Mala s 11 and Asp f 6. Bayesian Analysis suggest a high probability of the independent development of sensitization to different fungal allergens. The idea that sensitization to one allergen may be protective against sensitization to another one(s) requires further clinical study., (© 2024 The Authors.)

Fungal flora is one of the causes of inflammatory, including polypous, processes in the nasal cavity. In this regard, studies aimed at reducing the effect of fungal sensitization (FS) on the course of chronic polypous rhinosinusitis (CPRS) are relevant. The objective of the study was to evaluate the effect of various treatment options on the clinical course of the disease in patients with chronic polypous rhinosinusitis against the background of sensitization to fungi. The study included 90 patients with chronic polypous rhinosinusitis in combination with FS. The patients were divided into two groups - the first clinical group (G1) and the second clinical group (G2). G1 patients received allergen-specific immunotherapy (ASIT) according to the scheme. G2 patients received basic treatment. Evaluation of the clinical efficiency of ASIT was made based on complaints, assessment of symptom severity on a visual analog scale (VAS), and rhinoendoscopic examination. The treatment outcomes were evaluated on a 4-point scale, with excellent results (4 points) - complete remission of the disease during the follow-up period (6-12 months); good (3 points) - exacerbation of the disease 1-2 times a year, in mild form and removed by expectant treatment; satisfactory (2 points) - the number of exacerbations did not decrease. The use of ASIT therapy is pathogenetically justified and leads to a significant improvement in the clinical condition of patients with CPRS with FS. [ABSTRACT FROM AUTHOR]

Fungi have many potential roles in paediatric asthma, predominantly by being a source of allergens (severe asthma with fungal sensitization, SAFS), and also directly damaging the epithelial barrier and underlying tissue by releasing proteolytic enzymes (fungal bronchitis). The umbrella term ‘fungal asthma’ is proposed for these manifestations. Allergic bronchopulmonary aspergillosis (ABPA) is not a feature of childhood asthma, for unclear reasons. Diagnostic criteria for SAFS are based on sensitivity to fungal allergen(s) demonstrated either by skin prick test or specific IgE. In children, there are no exclusion criteria on total IgE levels or IgG precipitins because of the rarity of ABPA. Diagnostic criteria for fungal bronchitis are much less well established. Data in adults and children suggest SAFS is associated with worse asthma control and greater susceptibility to asthma attacks than non-sensitized patients. The data on whether anti-fungal therapy is beneficial are conflicting. The pathophysiology of SAFS is unclear, but the epithelial alarmin interleukin-33 is implicated. However, whether individual fungi have different pathobiologies is unclear. There are many unanswered questions needing further research, including how fungi interact with other allergens, bacteria, and viruses, and what optimal therapy should be, including whether anti-neutrophilic strategies, such as macrolides, should be used. Considerable further research is needed to unravel the complex roles of different fungi in severe asthma. [ABSTRACT FROM AUTHOR]

The U.S. Global Change Research Program, Fourth National Climate Assessment reports that it is extremely likely that human activities, especially emissions of greenhouse gases, are the dominant cause of the observed warming since the mid-20th century. There are no convincing alternative explanations supported by observational evidence., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fungal asthma broadly encompasses the presence of fungal sensitization or fungal allergy in patients with asthma. The clinical presentation of fungal asthma can vary from fungal-sensitized asthma at one end to allergic bronchopulmonary mycosis at the other end of the spectrum. Here we present five cases that illustrate some of the most challenging aspects of the diagnosis and management of fungal asthma. The cases are aimed at elucidating complex clinical presentations in fungal asthma such as allergic bronchopulmonary mycosis presenting with normal immunoglobulin E (IgE) values, the role of several different fungi in causing allergic mycosis, newer treatments like omalizumab (and mepolizumab), and a complication of long-standing allergic bronchopulmonary aspergillosis, namely, chronic pulmonary aspergillosis. [ABSTRACT FROM AUTHOR]

Aspergillus fumigatus is the most common Aspergillus species worldwide; however, A. flavus has also been shown to be prevalent in North India. Herein, we investigate the prevalence of sensitization to A. flavus in subjects with allergic bronchopulmonary aspergillosis (ABPA). We also evaluate the occurrence of allergic bronchopulmonary mycosis (ABPM) due to A. flavus. Treatment-naive subjects with ABPA underwent sputum culture; and, skin testing, fungal-specific immunoglobulin E (IgE) and serum precipitation tests for A. fumigatus and A. flavus. Sensitization to A. flavus was diagnosed if any immunological test for A. flavus was positive in subjects with ABPA. ABPM was labelled as probable if sputum cultures grew A. flavus and A. flavus -specific IgE was greater than A. fumigatus -specific IgE; and, possible if only A. flavus -specific IgE was greater than A. fumigatus -specific IgE. Fifty-three subjects with a mean (SD) age of 34.2 (12.8) years were included. Sensitization to A. flavus was seen in 51 (96.2%) subjects, with overlap occurring in 49 (92.5%), 21 (39.6%), and 12 (22.6%) instances on fungal-specific IgE, skin prick test and precipitins, respectively. Sputum culture was positive in 18 (33.9%; A. flavus [ n = 12], A. fumigatus [ n = 6]) subjects. ABPM due to A. flavus was diagnosed in 16 (30.2%) subjects (10 probable, 6 possible). They were more likely to have high-attenuation mucus and a trend towards higher occurrence of sinusitis, compared to ABPA. We found a high occurrence of sensitization to A. flavus in subjects with ABPA. Subjects with A. flavus -related ABPM had a higher likelihood of high-attenuation mucus and probability of sinusitis. More studies are required to confirm this observation. [ABSTRACT FROM AUTHOR]

Fungi have many potential roles in paediatric asthma, predominantly by being a source of allergens (severe asthma with fungal sensitization, SAFS), and also directly damaging the epithelial barrier and underlying tissue by releasing proteolytic enzymes (fungal bronchitis). The umbrella term ‘fungal asthma’ is proposed for these manifestations. Allergic bronchopulmonary aspergillosis (ABPA) is not a feature of childhood asthma, for unclear reasons. Diagnostic criteria for SAFS are based on sensitivity to fungal allergen(s) demonstrated either by skin prick test or specific IgE. In children, there are no exclusion criteria on total IgE levels or IgG precipitins because of the rarity of ABPA. Diagnostic criteria for fungal bronchitis are much less well established. Data in adults and children suggest SAFS is associated with worse asthma control and greater susceptibility to asthma attacks than non-sensitized patients. The data on whether anti-fungal therapy is beneficial are conflicting. The pathophysiology of SAFS is unclear, but the epithelial alarmin interleukin-33 is implicated. However, whether individual fungi have different pathobiologies is unclear. There are many unanswered questions needing further research, including how fungi interact with other allergens, bacteria, and viruses, and what optimal therapy should be, including whether anti-neutrophilic strategies, such as macrolides, should be used. Considerable further research is needed to unravel the complex roles of different fungi in severe asthma.

Differences in the clinical phenotypes and outcomes of fungus-associated asthma remain unclear. We aimed to investigate the presentation of asthmatics with fungal sensitization and/or positive fungal isolates. Clinical characteristics, pulmonary function, microbiological data, allergy test reports, emergency department (ED) visits and hospitalizations were retrieved from the Chang Gung Research Database between 2010 and 2018; the largest electronic medical record-based database in Taiwan. Follow-up care was provided to each patient for 3 years. A total of 30,754 asthmatics were enrolled, and 7976 were eligible for analysis after applying the exclusion criteria. Of these patients, 694 had sputum examinations for fungi. The patients were divided into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n = 386); group 2, positive fungal sensitization (n = 58); group 3, positive fungal isolates (n = 217); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n = 33). Asthmatic patients with fungal sensitization (groups 2 and 4) demonstrated significantly higher IgE levels compared with those without (groups 1 and 3). Group 4 patients had a higher frequency of hospitalization. Amongst patients under Global Initiative for Asthma (GINA) step 4–5 therapies, group 4 asthmatics possessed significantly higher incidence of respiratory failure. The prevalence of fungal sensitization and fungal isolates from sputum were even across asthmatic severities, but the clinical impact of fungi may be more significant among patients with more severe disease. [ABSTRACT FROM AUTHOR]

Background: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients remains unclear and is likely different across geographic locales., Objective: To systematically review the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in adults with bronchial asthma., Methods: We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in at least 50 asthmatic subjects. The primary outcome was to assess the prevalence of ABPA. The secondary outcome was to evaluate the prevalence of AS in asthma and that of ABPA in asthma with AS. We pooled the prevalence estimates using a random-effects model and examined the factors influencing the prevalence using multivariate meta-regression., Results: Of the 11,801 records retrieved, 86 studies with 25,770 asthmatic subjects met the inclusion criteria. Most of the studies were from tertiary care centers. The pooled prevalence of ABPA in asthma (47 studies; 9822 asthmatic subjects) was 11.3% (95% CI, 8.7-14.2). The pooled prevalence of AS in asthma (73 studies; 23,003 asthmatic subjects) was 25.1% (95% CI, 20.5-30.0), whereas the prevalence of ABPA in AS (36 studies; 2954 asthmatic subjects) was 37.0% (95% CI, 27.9-46.6). Multivariate meta-regression identified studies published from India (odds ratio, 1.11; 95% CI, 1.01-1.23) as the only factor associated with higher ABPA prevalence. There was presence of significant statistical heterogeneity and publication bias., Conclusions: We found a high prevalence of ABPA in adult asthmatic subjects, underscoring the need for screening for ABPA in all asthmatic subjects seeking tertiary care., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background The prevalence of Aspergillus sensitization ( AS) and allergic bronchopulmonary aspergillosis ( ABPA) in cystic fibrosis ( CF) has been varyingly reported. The aim of this systematic review was to estimate the overall prevalence of AS/ ABPA in CF. Methods We searched the PubMed and EmBase databases for studies reporting the prevalence of AS/ ABPA in CF. We calculated the proportion with 95% confidence interval ( CI) to assess the prevalence of AS and ABPA in the individual studies and then pooled the results using a random effects model. Statistical heterogeneity was assessed using the I2 test while publication bias was assessed using both graphical and statistical methods. Results Our search yielded 64 eligible studies. The pooled prevalence of AS was 39.1% (95% CI: 33.3-45.1) and was higher with skin test compared to specific IgE (43.8% vs. 32.8%, P = 0.002); however, the prevalence did not vary with the type of skin test used (intradermal or percutaneous). The prevalence of ABPA was 8.9% (95% CI: 7.4-10.7) and was higher in adults as compared to children (10.1% vs. 8.9%, P < 0.0001). There was a wide variation in the criteria used for diagnosing ABPA. Almost 50% (12/23) of the publications after 2004 used criteria other than the CF foundation criteria for diagnosing ABPA. There was significant statistical heterogeneity and evidence of publication bias. Conclusions There is a high prevalence of AS and ABPA in patients with CF. Despite six decades of research, there is still a need to adopt uniform methodology and criteria for the diagnosis of AS/ ABPA. [ABSTRACT FROM AUTHOR]

Although fungi are pervasive in many environments, few cause disease in humans. Of these, Aspergillus fumigatus is particularly well suited to be a pathogen of the human lung. Its physical and biological characteristics combine to provide an organism that can cause tremendous morbidity and high mortality if left unchecked. Luckily, that is rarely the case. However, repeated exposure to inhaled A. fumigatus spores often results in an immune response that carries significant immunopathology, exacerbating asthma and changing the structure of the lung with chronic impacts to pulmonary function. This review focuses on the current understanding of the mechanisms that are associated with fungal exposure, sensitization, and infection in asthmatics, as well as the function of various inflammatory cells associated with severe asthma with fungal sensitization. [ABSTRACT FROM AUTHOR]

Background: To investigate the modulation of B-cell-activating factor (BAFF) expression on the basophil membrane of allergic patients. BAFF is an important regulator of B-cell activation, proliferation and immunoglobulin production, which may play a role in respiratory allergic diseases in promoting the production of IgE by B cells. Methods: Peripheral blood samples of 10 patients with allergic rhinitis, 3 with severe asthma and fungal sensitization (SAFS), 3 with allergic bronchopulmonary aspergillosis (ABPA) and 11 healthy controls were assessed regarding BAFF (CD257) expression using the basophil activation test before and after stimulation with IgE and allergens, as well IgE-independent stimuli, like fMLP, lipotheichoic acid from Staphylococcus aureus (LTA-SA) and lipopolysaccharide (LPS). Results: BAFF membrane expression did not change after IgE and allergen stimulation both in patients and controls, while it was upregulated by Aspergillus stimulation, both in sensitized patients and controls. In both patients and controls, BAFF expression was significantly upregulated following LTA-SA and β-1,3-glucan exposure (toll-like receptor-2 ligands), but not following LPS stimulation. Conclusions: Basophils from allergic and healthy subjects constitutively express membrane BAFF, which is not upregulated by IgE or specific allergens but by TLR-2 ligands (LTA-SA and β-1,3-glucan). Aspergillus fumigatus stimulation was able to upregulate BAFF expression on the basophils of sensitized asthmatic patients, but not via IgE-dependent mechanisms, since results did not differ between the patient and control groups. These findings suggest that basophils may contribute to the polyclonal production of IgE commonly observed in patients with SAFS and ABPA. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Allergic bronchopulmonary aspergillosis (ABPA) is an insidious pulmonary disorder caused by hypersensitivity reactions mounted against Aspergillus fumigatus. Usually, complicating the course of patients with asthma and cystic fibrosis, the affliction has recently been described in chronic obstructive pulmonary disease and pulmonary tuberculosis-related fibrocavitary disease. Patients commonly present with poorly controlled asthma, recurrent pulmonary infiltrates and bronchiectasis. More than six decades have elapsed since the first description of this entity; however, the condition remains poorly understood. The International Society for Human and Animal Mycology has formed a working group to address the deficiencies associated with understanding of this disorder. New criteria have been laid down for diagnosis and staging of the disorder, so as to simplify the identification and management of this condition. This review summarizes the recent advances that have taken place in this condition with special emphasis on the burden and distinct character of ABPA in the Indian subcontinent. [ABSTRACT FROM AUTHOR]