Very high serum IgE (≥1000 IU/mL) is reported in atopic disorders. However, data on its significance in nonallergic disorders are limited.

We aimed to analyze the diagnostic value of very high IgE in adults.

A retrospective nationwide study was conducted using the electronic database of Clalit Health Services, covering adults (≥18 years) treated between 2002 and 2022. Subjects with IgE ≥ 1000 IU/mL were compared to the controls with IgE < 100 IU/mL across 3 age groups (18-30, 31-64, and ≥65 years). Outcomes included eosinophilic, autoimmune, autoinflammatory, and cardiovascular disorders (CVD), cancer, and inborn errors of immunity (IEI). A multivariable Cox regression model determined statistical significance (P < .05).

The study included 118,211 subjects: 110,116 controls and 8635 with very high IgE levels. Excluding insect sting and drug allergies, very high IgE was more common across all tested allergic disorders, with asthma showing the highest rate (64.49%). Univariable analysis showed higher prevalence of CVD (3.88% vs 2.72%, P < .001), eosinophilic disorders (0.42% vs 0.06%, P < .001), and IEI (0.35% vs 0.20%, P = .004) in the very high IgE group. Multivariable analysis revealed age-dependent significant results: higher CVD risk in ages 31-64 (hazard ratio = 1.249; 95% confidence interval, 1.054-1.481; P = .010) and borderline IEI association in ages 18-30 (hazard ratio = 1.802; 95% confidence interval, 0.978-3.321; P = .059). Risk of eosinophilic disorders was increased across all age groups (P < .001).

Very high IgE level of ≥1000 IU/mL is associated with increased risks of CVD, IEI, and eosinophilic disorders. Physicians should consider further assessment for these conditions in nonallergic patients with very high IgE levels.

Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a severe hypersensitivity reaction to Aspergillus species. Current treatment relies on oral corticosteroids (OCS) and triazole antifungal therapy, but there is increasing evidence of the benefits of biologic therapies targeting type 2 inflammatory pathways.

To assess the real-world effectiveness of biologic therapies in patients with ABPA.

We performed a large retrospective single-center analysis of patients with ABPA as defined by the modified International Society for Human and Animal Mycology (ISHAM) criteria between 2014 and 2022. Baseline characteristics were recorded. Clinical outcomes were assessed at 12 months after commencement of a biologic including symptom scores, exacerbation frequency, corticosteroid use, and multidisciplinary team consensus of effectiveness.

A total of 74 patients received a biologic, of whom 32% (n = 24) received anti-IgE therapy, 65% (n = 48) anti-IL5/5Rα therapy, and 3% (n = 2) anti-IL4-Rα therapy. Of the total, 65% (n = 48) patients were deemed to have a successful response at 12 months with a ≥50% reduction in OCS use and 35% (n = 26) stopped or changed biologic during the follow-up period because of failed clinical response (n = 21), side effects (n = 4), or medical comorbidities (n = 1). There was a significant reduction in the 6-item Asthma Control Questionnaire score (P < .0001), exacerbation rate over 12 months (P < .0001), and maintenance OCS use (P = .0173). Univariate analysis revealed that mucus plugging was associated with nonresponse to biologic therapy (P = .0189).

Biologic therapies are effective in a number of patients with ABPA. However, further prospective clinical trials are required to determine the effectiveness and which phenotypes likely to respond. These data nevertheless increase the evidence base for biologics in ABPA.

The clinical significance of co-infection with chronic pulmonary aspergillosis (CPA) and bacteria is limited and has mostly been studied in specific patient groups. This study aims to investigate the incidence and prognostic impact of bacterial co-infection in patients with CPA.

A single-center, retrospective, observational study was conducted between 2019 and 2024. Patients were categorized based on the presence of bacterial co-infection, and their demographics, potential underlying factors, and prognosis were analyzed.

A total of 101 patients were included (mean age: 57 ± 13 years, 79 male). Bacterial co-infection was identified in 21 patients (21%). The most common bacterial pathogens at diagnosis were Pseudomonas aeruginosa (n = 6), Klebsiella pneumoniae (n = 5), Escherichia coli (n = 4), and Serratia marcescens (n = 4). Five patients had a history of prior bacterial colonization. At diagnosis, more than one bacterial species were identified in six patients. Sputum production and hypoxemic respiratory failure were more frequently observed in patients with bacterial co-infection. Systemic corticosteroid use was more common in the co-infected group. However, radiological findings and diagnostic procedures did not differ between the groups. Surgical interventions were more commonly performed in the non-co-infected group. During the follow-up, hospital admission rates, mortality, and overall survival were comparable between the two groups.

Bacterial co-infections are probable in CPA and follow-up results of both patient Groups may not differ. Timely diagnosis and close follow-up of these patients are probable key factors in these patients.

Fungal pericarditis is a rare disease but its incidence has risen in parallel with the global increase in invasive fungal infections. This systematic review analyzes data from previously reported cases of fungal pericarditis to provide an improved understanding of the etiology, clinical presentation, management, and outcomes of this rare disease. We reviewed Medline and Scopus databases from 1 January 1990 to 29 January 2024 for case reports that documented the isolation of a fungal pathogen from pericardial fluid or tissue. Of the 2330 articles screened, 101 cases met the inclusion criteria. Patients with fungal pericarditis and the involvement of at least one other organ-usually the lungs, brain, or kidney-had worse outcomes than patients with isolated pericardial disease. Immunosuppression was reported in 50% of cases and was associated with worse outcomes in adults. Patients who presented with chest pain, received adequate empiric antifungal therapy, and underwent pericardiocentesis and pericardiectomy had improved survival. The most common isolated pathogens were Candida spp., followed by Aspergillus spp. and Mucor spp., with the latter two linked to worse outcomes. Only 35% of patients received empiric antifungal medications before the causative pathogen was identified, and mortality was associated with a delay in appropriate therapy. Immunosuppression, disseminated disease, and presence of shock/multiorgan failure were additional risk factors associated with death. Fungal pericarditis carries a mortality rate of up to 50%, with nearly half of patients being immunocompromised. Clinicians frequently do not consider fungal pericarditis in the differential diagnoses, which leads to delays in treatment and poorer outcomes. Further prospective multicenter studies are urgently needed to better understand the epidemiology, improve diagnostic testing and management, and decrease unacceptably high mortality in patients with fungal pericarditis.

Allergic bronchopulmonary aspergillosis is an incurable disease caused by the environmental mold Aspergillus fumigatus. This hypersensitivity pneumonia is characterized by an inflammatory type 2 immune response, accompanied by influx of eosinophils into the lung. To investigate the mode of action of eosinophils and the signaling events triggered by A. fumigatus, we used an in vitro coculture system of murine bone marrow-derived eosinophils confronted with conidia. Using small-molecule inhibitors, we identified signaling modules of eosinophils in the course of A. fumigatus confrontation. Eosinophils reduced fungal metabolic activity, but inhibition of relevant signaling modules did not affect this phenomenon upon eosinophil confrontation. A. fumigatus-induced secretion of Th2 cytokines and chemokines by eosinophils engaged proto-oncogene tyrosine-protein kinase Src, phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase as well as calcium cations and to some extent serine/threonine-protein kinase Akt and protein arginine deiminase 4. Src and PI3K kinases were also involved in A. fumigatus-mediated ROS production and regulation of eosinophils surface receptors. Especially Src and PI3K inhibitors prevented A. fumigatus-induced eosinophil activation. Taken together, identification of signaling cascades of eosinophils during their interaction with A. fumigatus provides relevant insights into the host-pathogen interaction in the context of ABPA to yield therapeutic perspectives.

The role of 2-deoxy-2-18(F) fluoro-D-glucose (FDG) positron emission tomography (PET)-computed tomography (CT) in assessing treatment response in chronic pulmonary aspergillosis (CPA) remains to be determined. The study objective was to compare FDG-PET/CT parameters in persons with CPA achieving treatment success or failure after 6 months of oral itraconazole.

We performed PET-CT at baseline and after 6 months of oral itraconazole therapy. FDG uptake similar to the background uptake or ≥13 units decline in Z-score was considered a complete metabolic response (CMR). A >25%, >30%, and > 45% decline in standardised uptake value (SUVmax), SUVpeak, and total glycolytic activity (TLG) was labelled as a partial metabolic response (PMR). A >30%, >30%, or >75% increase in the SUVmax, SUVpeak, and TLG represented progressive metabolic disease.

We included 94 persons with CPA (63 male) with a mean age of 46.2 years. A follow-up PET-CT was performed on 77 participants. We recorded treatment success and failure in 43 and 34 patients. CMR was seen in 18.6% of those with treatment success and none with treatment failure. A higher proportion of patients with treatment success achieved PMR; 19% of the patients with treatment success had progressive metabolic disease.

Most PET-CT parameters improved with treatment; however, PET-CT misclassified one-fifth of the participants.

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.

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.

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.

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.

The airborne fungus Aspergillus fumigatus is a major pathogen that poses a serious health threat to humans by causing aspergillosis. Azole antifungals inhibit sterol 14-demethylase (encoded by cyp51A), an enzyme crucial for fungal cell survival. However, the most common mechanism of azole resistance in A. fumigatus is associated with the mutations in cyp51A and tandem repeats in its promoter, leading to reduced drug-enzyme interaction and overexpression of cyp51A. It remains unknown whether post-translational modifications of Cyp51A contribute to azole resistance. In this study, we report that the Cyp51A expression is highly induced upon exposure to itraconazole, while its ubiquitination level is significantly reduced by itraconazole. Loss of the ubiquitin-conjugating enzyme Ubc7 confers resistance to multiple azole antifungals but hinders hyphal growth, conidiation, and virulence. Western blot and immunoprecipitation assays show that deletion of ubc7 reduces Cyp51A degradation by impairing its ubiquitination, thereby leading to drug resistance. Most importantly, the overexpression of ubc7 in common environmental and clinical azole-resistant cyp51A isolates partially restores azole sensitivity. Our findings demonstrate a non-cyp51A mutation-based resistance mechanism and uncover a novel role of post-translational modification in contributing to azole resistance in A. fumigatus.

The surveillance of serious and superficial skin fungal infections in Iraq has not been conducted. Limited information exists on their incidence and prevalence.

This study aimed to analyze, compute and estimate the prevalence and burden of fungal infections, as no previous data is available and no studies has been attempted in Iraq.

In the present study the data were collected and reviewed from published data on epidemiology of fungal infections nationally, internationally, from unpublished postgraduate master and PhD theses, hospital records and private clinic records. External sources of data from other countries were used for diseases which lacked sufficient local data.

We estimated 985,628 annual serious infections comprising of 2.26 % of the total population. When including superficial fungal infections group of the skin, this rises to 2,075,113 infections at 4.76 % of the total population. The most common serious and skin infections were recurrent Candida vaginitis, fungal rhinosinusitis and tinea capitis comprising 61.5 %, 21.8 %, and 22.4 % of all infections although the total incidence of superficial fungal infections was also high at 1,071,485. Respiratory fungal disease is also common comprising 14.0 % of infections. We predicted the following annual burden per 100,000; oral candidiasis at 247.9, esophageal candidiasis at 6.04, candidemia at 5.0, Candida peritonitis at 0.75, recurrent Candida vaginitis at 5461, allergic bronchopulmonary aspergillosis at 35, severe asthma with fungal sensitisation at 46, invasive aspergillosis at 7.9, chronic pulmonary aspergillosis at 11.7, chronic fungal rhinosinusitis at 496, mucormycosis at 0.99, fungal keratitis at 14.0, and total dermatophytosis at 1631, the most severe being tinea capitis at 366. Many of these estimates were made with data sourced from other nations, so additional data from Iraq is required to validate or modify these estimates.

Recurrent Candida vaginitis, fungal rhinosinusitis, and tinea capitis are considered to be the most frequent fungal diseases present in Iraq.

Allergic bronchopulmonary aspergillosis (ABPA) is a rare airway disorder primarily affecting patients with asthma and cystic fibrosis. Persistent airway inflammation brought on by Aspergillus fumigatus exacerbates the underlying condition and can cause significant respiratory damage. Treatments center on reducing inflammation with the use of corticosteroids and antifungals. PANoptosis is a new concept in the field of cell death and inflammation that posits the existence of cross talk and a master control system for the 3 programmed cell death (PCD) pathways, namely, apoptosis, pyroptosis, and necroptosis. This concept has revolutionized the understanding of PCD and opened new avenues for its exploration. Studies show that Aspergillus is one of the pathogens that is capable of activating PANoptosis via the Z-DNA binding protein 1 (ZBP1) pathway and plays an active role in the inflammation caused by this organism.

This article explores the nature of inflammation in ABPA and ways in which PCD could lead to novel treatment options.

PubMed was used to review the literature surrounding Aspergillus infection-related inflammation and PANoptosis.

There is evidence that apoptosis and pyroptosis protect against Aspergillus-induced inflammation, whereas necroptosis promotes inflammation.

Experimental medications, in particular, necroptosis inhibitors such as necrosulfonamide and necrostatin-1, should be studied for use in the treatment of ABPA.

Chronic pulmonary aspergillosis (CPA) has recently gained attention owing to its substantial health burden. However, the precise epidemiology and prognosis of the disease are still unclear due to the lack of a nationwide descriptive analysis. This study aimed to elucidate the epidemiology of patients with CPA and to investigate their prognosis.

Using a national administrative database covering >99% of the population in Japan, we calculated the nationwide incidence and prevalence of CPA from 2016 to 2022. Additionally, we clarified the survival rate of patients diagnosed with CPA and identified independent prognostic factors using multivariate Cox proportional hazard analysis.

During the study period, while the prevalence of CPA remained stable at 9.0-9.5 per 100,000 persons, its incidence declined to 2.1 from 3.5 per 100,000 person-years. The 1-, 3-, and 5-year survival rates were 65%, 48%, and 41%, respectively. During the year of CPA onset, approximately 50% of patients received oral corticosteroids (OCS) at least once, while about 30% underwent frequent OCS treatment (≥4 times per year) within the same timeframe. Increased mortality was independently associated with older age (>65 years) (hazard ratio [HR], 2.65; 95% confidence interval (CI), 2.54-2.77), males (1.24; 1.20-1.29), a history of chronic obstructive pulmonary disease (1.05; 1.02-1.09), lung cancer (1.12; 1.06-1.18); and ILD (1.19; 1.14-1.24); and frequent OCS use (1.13; 1.09-1.17). Conversely, decreased mortality was associated with a history of tuberculosis (HR, 0.81; 95% CI, 0.76-0.86), non-tuberculous mycobacteria (0.91; 0.86-0.96), and other chronic pulmonary diseases (0.89; 0.85-0.92).

The incidence of CPA decreased over the past decade, although the prevalence was stable and much higher than that in European countries. Moreover, the patients' prognosis was poor. Physicians should be vigilant about CPA onset in patients with specific high-risk underlying pulmonary conditions.

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.

Bronchiectasis is a chronic respiratory disease characterised by permanent enlargement of the airways associated with cough, sputum production and a history of pulmonary exacerbations. In the past few years, incidence and prevalence of bronchiectasis have increased worldwide, possibly due to advances in imaging techniques and disease awareness, leading to increased socioeconomic burden and healthcare costs. Consistently, a mortality increase in bronchiectasis patient cohorts has been demonstrated in certain areas of the globe, with mortality rates of 16-24.8% over 4-5 years of follow-up. However, heterogeneity in epidemiological data is consistent, as reported prevalence in the general population ranges from 52.3 to more than 1000 per 100 000. Methodological flaws in the designs of available studies are likely to underestimate the proportion of people suffering from this condition worldwide and comparisons between different areas of the globe might be unreliable due to different assessment methods or local implementation of the same method in different contexts. Differences in disease severity associated with diverse geographical distribution of aetiologies, comorbidities and microbiology might explain an additional quota of heterogeneity. Finally, limited access to care in certain geographical areas is associated with both underestimation of the disease and increased severity and mortality. The aim of this review is to provide a snapshot of available real-world epidemiological data describing incidence and prevalence of bronchiectasis in the general population. Furthermore, data on mortality, healthcare burden and high-risk populations are provided. Finally, an analysis of the geographical distribution of determinants contributing to differences in bronchiectasis epidemiology is offered.

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.

Antimicrobial resistance is a major global threat. In an attempt to discover new compounds with improved efficiency and to overcome drug resistance, a library of 3960 compounds was designed as conformationally rigid analogues of oxiconazole with 2H-chroman-4-one, azole and substituted phenyl fragments. The antifungal and antibacterial activity of the compounds was evaluated using molecular docking studies in the active site of six fungal and four bacterial proteins to establish the binding affinity of the designed ligands. In-silico ADME and Lipinski's rule were used to establish the drug-likeness properties of the compounds. This study revealed that all the designed compounds had a high binding affinity with the target proteins and formed H-bond and π-π interactions. The identified hits have been subjected to molecular dynamics simulations to study protein-ligand complex stability. This study has led to the identification of important compounds that can be developed further as therapeutic agents against pathogenic fungi and bacteria.Communicated by Ramaswamy H. Sarma.

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.

An 80-year-old woman who developed allergic bronchopulmonary aspergillosis (ABPA) was admitted to our institution in 2023 for an enlarged pulmonary mass lesion. She had developed ABPA in 2017, and corticosteroid therapy had improved the mucoid impaction of the bronchi. Because part of the lesion remained, increased doses of corticosteroid, antifungals, and biologics were administered, but the pulmonary lesion enlarged in 2022. Bronchoscopy showed necrotic tissue in the bronchial lumen, and bronchial washing fluid showed neutrophilic inflammation and fungal hyphae. We subsequently diagnosed her as having chronic pulmonary aspergillosis overlapping ABPA, and voriconazole was started that resulted in shrinkage of the nodules.

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.

Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed countries, eosinophilic inflammation is strongly associated with allergic/sterile inflammation, and constitutes an undesired immune reaction. This situation is in stark contrast to neutrophilic inflammation, which is indispensable for the host defense against bacterial infections. Among eosinophilic inflammatory disorders, massive accumulation of eosinophils within mucus is observed in certain cases, and is often linked to the distinctive clinical finding of mucus with high viscosity. Eosinophilic mucus is found in a variety of diseases, including chronic allergic keratoconjunctivitis, chronic rhinosinusitis encompassing allergic fungal sinusitis, eosinophilic otitis media, eosinophilic sialodochitis, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic plastic bronchitis, and eosinophilic asthma. In these pathological conditions, chronic inflammation and tissue remodeling coupled with irreversible organ damage due to persistent adhesion of toxic substances and luminal obstruction may impose a significant burden on the body. Eosinophils aggregate in the hyperconcentrated mucus together with cell-derived crystals, macromolecules, and polymers, thereby affecting the biophysical properties of the mucus. This review focuses on the clinically significant challenges of mucus and discusses the consequences of activated eosinophils on the mucosal surface that impact mucus and persistent inflammation.

Fungal infections are a significant global health problem, particularly affecting individuals with weakened immune systems. Moreover, as uncontrolled antibiotic and immunosuppressant use increases continuously, fungal infections have seen a dramatic increase, with some strains developing antibiotic resistance. Traditional approaches to identifying fungal strains often rely on morphological characteristics, thus owning limitations, such as struggles in identifying several strains or distinguishing between fungal strains with similar morphologies. This review explores the multifaceted impact of fungi infections on individuals, healthcare providers, and society, highlighting the often-underestimated economic burden and healthcare implications of these infections. In light of the serious constraints of traditional fungal identification methods, this review discusses the potential of plasmonic nanoparticle-based biosensors for fungal infection identification. These biosensors can enable rapid and precise fungal pathogen detection by exploiting several readout approaches, including various spectroscopic techniques, colorimetric and electrochemical assays, as well as lateral-flow immunoassay methods. Moreover, we report the remarkable impact of plasmonic Lab on a Chip technology and microfluidic devices, as they recently emerged as a class of advanced biosensors. Finally, we provide an overview of smartphone-based Point-of-Care devices and the associated technologies developed for detecting and identifying fungal pathogens.

Current estimates of fungal disease incidence and mortality are imprecise. Population at risk denominators were used to estimate annual incidence for 2019-21. Extensive literature searches from 2010 to 2023 were combined with over 85 papers on individual country and global disease burden. Crude and attributable mortality were estimated using a combination of untreated mortality, the proportion of patients who are treated, and percentage survival in treated patients. Awareness, guidelines, and accessibility of diagnostics and therapies informed the ratio of treated to untreated cases. Estimates do not include influenza or COVID-19 outbreaks. Data from more than 120 countries were included. Annually, over 2 113 000 people develop invasive aspergillosis in the context of chronic obstructive pulmonary disease, intensive care, lung cancer, or haematological malignancy, with a crude annual mortality of 1 801 000 (85·2%). The annual incidence of chronic pulmonary aspergillosis is 1 837 272, with 340 000 (18·5%) deaths. About 1 565 000 people have a Candida bloodstream infection or invasive candidiasis each year, with 995 000 deaths (63·6%). Pneumocystis pneumonia affects 505 000 people, with 214 000 deaths (42·4%). Cryptococcal meningitis affects 194 000 people, with 147 000 deaths (75·8%). Other major life-threatening fungal infections affect about 300 000 people, causing 161 000 deaths (53·7%). Fungal asthma affects approximately 11·5 million people and might contribute to 46 000 asthma deaths annually. These updated estimates suggest an annual incidence of 6·5 million invasive fungal infections and 3·8 million deaths, of which about 2·5 million (68%; range 35-90) were directly attributable.

Allergic bronchopulmonary aspergillosis and invasive fungal diseases represent distinct infectious entities that cause significant morbidity and mortality. Currently, administered inhaled antifungal therapies are unapproved, have suboptimal efficacy, and are associated with considerable adverse reactions. The emergence of resistant pathogens is also a growing concern. Inhaled antifungal development programs are challenged by inadequate nonclinical infection models, highly heterogenous patient populations, low prevalence rates of fungal diseases, difficulties defining clinical trial enrollment criteria, and lack of robust clinical trial endpoints. On 25 September 2020, the US Food and Drug Administration (FDA) convened a workshop with experts in pulmonary medicine and infectious diseases from academia, industry, and other governmental agencies. Key discussion topics included regulatory incentives to facilitate development of inhaled antifungal drugs and combination inhalational devices, limitations of existing nonclinical models and clinical trial designs, patient perspectives, and industry insights.

With increasing concern about the negative health impact of fungal disease, there is a need to survey what is and is not known about the epidemiology of these infections in Tunisia. We have estimated the incidence and prevalence of the most serious fungal diseases in Tunisia for the first time. Using published literature from Tunisia, or if absent other countries, we have estimated the burden of life-threatening fungal infections and those causing significant morbidity, using deterministic modeling, based on populations at greatest risk. An estimated 250,494 (2.12% of the Tunisian population) are affected by a serious fungal disease annually. Invasive and chronic pulmonary aspergillosis are relatively common with 708 and 2090 patients affected, partly linked to the prevalence of chronic obstructive pulmonary disease (COPD). Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization) have an estimated prevalence of 38,264 (5.8% of the adult asthma population). Fungal keratitis probably affects 1,761 eyes annually, often leading to uniocular blindness. Candidaemia and Candida peritonitis probably affect at least 680 people annually, with a high mortality. Recurrent vulvovaginal candidiasis probably affects over 200,000 women. While fungal diseases are regularly diagnosed in Tunisia, epidemiological studies with denominators are uncommon. Some fungal diseases are poorly addressed with the current diagnostic portfolio, and surveillance is lacking. Studies on these diseases and the implementation of a national program of surveillance are required.

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.

Fosmanogepix, a prodrug of Manogepix (MGX), is a groundbreaking antifungal agent with broad-spectrum activity against yeasts, including Cryptococcus and Candida, as well as molds. It exhibits effectiveness against drug-resistant strains, such as Candida strains resistant to echinocandins and Aspergillus strains resistant to azoles. Furthermore, fosmanogepix shows activity against pathogens that typically resist other classes of drugs, such as Scedosporium, Lomentospora prolificans, and Fusarium, although its efficacy against Mucorales varies. In animal models, fosmanogepix has demonstrated notable effectiveness against disseminated infections caused by various Candida species, Coccidioides immitis, and Fusarium solani. It has also shown efficacy in pulmonary infection models involving Aspergillus fumigatus, Aspergillus flavus, Scedosporium prolificans, Scedosporium apiospermum, and Rhizopus arrhizus. Clinical trials have revealed excellent oral bioavailability (>90%), enabling a seamless transition between intravenous and oral formulations without compromising blood concentrations. Fosmanogepix exhibits favorable profiles in terms of drug interactions, tolerability, and extensive distribution in various tissues, making it an appealing choice for treating invasive fungal infections. This comprehensive review aims to examine the outcomes of published data on fosmanogepix, encompassing in vitro, in vivo, and clinical investigations.

The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics.

An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively.

We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response.

We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Data published on Panamanian fungal disease are scarce, mostly case reports. To date, there is no paper that compiles the burden of fungal disease Here we estimate for the first time the incidence and prevalence of fungal diseases in Panama. Data on fungal disease were obtained from different search engines: PubMed, Google Scholar, Scielo and Lilacs. For population and at risk diseases, we used statistics from worldometer, UNAIDS, and WHO. Incidence, prevalence, and absolute numbers were calculated based on the population at risk. Panamanian population in 2022 was 4,429,739. We estimated that 85,530 (1.93 %) people suffer from fungal diseases. The most frequent fungal infection was recurrent Candida vaginitis (3285/100,000). There are 31,000 HIV-infected people in Panama and based on the number of cases not receiving anti-retroviral therapy (14,570), and previous reports of prevalence of opportunistic infections, we estimated annual incidences of 4.0/100,000 for cryptococcal meningitis, 29.5/100,000 for oral candidiasis, 23.1/100,000 for esophageal candidiasis, 29.5/100,000 for Pneumocystis pneumonia, 15.1/100,000, and for histoplasmosis. For chronic pulmonary aspergillosis (CPA) and fungal asthma we used data from Guatemala and Colombia to estimate COPD and asthma prevalence and WHO report for tuberculosis. We estimated annual incidences of 6.1/100,000 for invasive aspergillosis and prevalence of 31.5/100,000 for CPA, 60.2/100,000 for allergic bronchopulmonary aspergillosis, and 79.5/100,000 for severe asthma with fungal sensitisation. Other incidence estimates were 5.0/100,000 for candidaemia, 0.20/100,000 for mucormycosis, and 4.97/100,000 for fungal keratitis. Even though this report on burden of fungal disease is a forward step, more epidemiological studies to validate these estimates are needed.

Aspergillus species encompass a variety of infections, ranging from invasive aspergillosis to allergic conditions, contingent upon the immune status of the host. In this spectrum, Aspergillus terreus stands out due to its emergence as a notable pathogen and its intrinsic resistance to amphotericin-B. The significance of Aspergillus-associated infections has witnessed a marked increase in the past few decades, particularly with the increasing number of immunocompromised individuals. The exploration of epidemiology, morphological transitions, immunopathology, and novel treatment approaches such as new antifungal drugs (PC945, olorofim) and combinational therapy using antifungal drugs and phytochemicals (Phytochemicals: quercetin, shikonin, artemisinin), also using immunotherapies to modulate immune response has resulted in better outcomes. Furthermore, in the context COVID-19 era and its aftermath, fungal infections have emerged as a substantial challenge for both immunocompromised and immunocompetent individuals. This is attributed to the use of immune-suppressing therapies during COVID-19 infections and the increase in transplant cases. Consequently, this review aims to provide an updated overview encompassing the epidemiology, germination events, immunopathology, and novel drug treatment strategies against Aspergillus terreus-associated infections.

Aspergillus fumigatus is a ubiquitous opportunistic pathogen. This fungus can acquire resistance to azole antifungals due to different mutations in the cyp51A gene. Azole resistance has been observed in several continents and appears to be a globally distributed phenomenon. Specific mutations in cyp51A that lead to azole resistance, such as the TR34/L98H modification, have been reported.

To evaluate the azole resistance in clinically isolated A. fumigatus strains.

As a result of our passive surveillance strategy, a total of 23 A. fumigatus isolates from clinical origins were identified through a phylogenetic analysis using the ITS region and β-tubulin gene fragments, and typed with the CSP microsatellite. Azole susceptibility profiles were performed by disk diffusion and microdilution broth methodologies according to CLSI guidelines.

Here we describe, for the first time, the detection of azole-resistant A. fumigatus isolates from clinical origins in Chile with mutations in the cyp51A gene. In addition to the TR34/L98H mutation, one isolate exhibited an F46Y/M172V/E427K-type mutation. Furthermore, microsatellite typing based on cell surface protein (CSP) was performed, showing the t02 (TR34/L98H), t15 (F46Y/M172V/E427K) and t01 (susceptible clinical isolates) genotypes.

Our study demonstrates the presence of mutations related to azole resistance in A. fumigatus strains isolated from clinical samples in Chile. In order to obtain information that may help to tackle the spread of antifungal resistance among A. fumigatus populations, and to ensure the efficacy of future treatments against aspergillosis, a further research is necessary.

During recent decades, the emergence of pathogenic fungi has posed an increasing public health threat, particularly given the limited number of antifungal drugs available to treat invasive infections. In this Review, we discuss the global emergence and spread of three emerging antifungal-resistant fungi: Candida auris, driven by global health-care transmission and possibly facilitated by climate change; azole-resistant Aspergillus fumigatus, driven by the selection facilitated by azole fungicide use in agricultural and other settings; and Trichophyton indotineae, driven by the under-regulated use of over-the-counter high-potency corticosteroid-containing antifungal creams. The diversity of the fungi themselves and the drivers of their emergence make it clear that we cannot predict what might emerge next. Therefore, vigilance is critical to monitoring fungal emergence, as well as the rise in overall antifungal resistance.

Omalizumab is a valuable alternative treatment for allergic bronchopulmonary aspergillosis (ABPA). The effectiveness and safety of this medication have not been confirmed. The main purpose of this study was to evaluate the effectiveness and safety of omalizumab for ABPA.

This study involved a retrospective chart review. The main indicators used were asthma control test (ACT) scores, lung function parameters, doses of corticosteroids, acute exacerbation, hospitalization rates, total serum immunoglobulin E (IgE) levels, and blood eosinophil counts. Related adverse events were also reviewed to evaluate the safety of omalizumab.

Fourteen patients with ABPA were included, of whom 10 (71%) concurrently had allergic rhinitis (AR). There were improvements in the mean percentages of the forced vital capacity, percentages of the forced expiratory volume in 1 s, and ACT score after omalizumab administration (p < 0.05, p < 0.01, and p < 0.01, respectively). After the initiation of omalizumab administration, the median corticosteroid dose, acute exacerbation rate, hospitalization rate, and mean blood eosinophil count decreased when compared with the baseline values (p < 0.05, p < 0.05, p < 0.01, and p < 0.05, respectively). A reduction in the total serum IgE level was observed in patients with ABPA without AR compared with that in patients with AR (p < 0.05). One patient reported a concurrent skin rash, which spontaneously resolved without medication.

It is safe and effective to prescribe omalizumab to patients with ABPA, irrespective of whether they have AR. Dose adjustment of omalizumab is safe after disease control. The total serum IgE level might be a predictor of the effectiveness of omalizumab in patients without AR.

Poorly controlled asthma is especially common in low resource countries. Aside from lack of access to, or poor technique with, inhaled beta-2 agonists and corticosteroids, the most problematic forms of asthma are frequently associated with both fungal allergy and exposure, especially in adults leading to more asthma exacerbations and worse asthma. The umbrella term 'fungal asthma' describes many disorders linked to fungal exposure and/or allergy to fungi. One fungal asthma endotype, ABPA, is usually marked by a very high IgE and its differential diagnosis is reviewed. Both ABPA and fungal bronchitis in bronchiectasis are marked by thick excess airway mucus production. Dermatophyte skin infection can worsen asthma and eradication of the skin infection improves asthma. Exposure to fungi in the workplace, home and schools, often in damp or water-damaged buildings worsens asthma, and remediation improves symptom control and reduces exacerbations. Antifungal therapy is beneficial for fungal asthma as demonstrated in nine of 13 randomised controlled studies, reducing symptoms, corticosteroid need and exacerbations while improving lung function. Other useful therapies include azithromycin and some biologics approved for the treatment of severe asthma. If all individuals with poorly controlled and severe asthma could be 'relieved' of their fungal allergy and infection through antifungal therapy without systemic corticosteroids, the health benefits would be enormous and relatively inexpensive, improving the long term health of over 20 million adults and many children. Antifungal therapy carries some toxicity, drug interactions and triazole resistance risks, and data are incomplete. Here we summarise what is known and what remains uncertain about this complex topic.