Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans.

Th17 cells provide protection at barrier tissues but may also contribute to immune pathology. The relevance and induction mechanisms of pathologic Th17 responses in humans are poorly understood. Here, we identify the mucocutaneous pathobiont Candida albicans as the major direct inducer of human anti-fungal Th17 cells. Th17 cells directed against other fungi are induced by cross-reactivity to C. albicans. Intestinal inflammation expands total C. albicans and cross-reactive Th17 cells. Strikingly, Th17 cells cross-reactive to the airborne fungus Aspergillus fumigatus are selectively activated and expanded in patients with airway inflammation, especially during acute allergic bronchopulmonary aspergillosis. This indicates a direct link between protective intestinal Th17 responses against C. albicans and lung inflammation caused by airborne fungi. We identify heterologous immunity to a single, ubiquitous member of the microbiota as a central mechanism for systemic induction of human anti-fungal Th17 responses and as a potential risk factor for pulmonary inflammatory diseases.

Allergic bronchopulmonary aspergillosis in a lung transplant recipient treated with mepolizumab.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus spp. ABPA diagnosis may be challenging due to its non-specific presentation. Standard ABPA treatment consists of systemic corticosteroids and antifungal agents. Mepolizumab, a monoclonal antibody against interleukin-5 seems to be a promising treatment for ABPA. Data about ABPA following lung transplantation (LuTx) are scarce. LuTx recipients are at higher risk for adverse effects of ABPA treatment compared to the general population. Here we present a case of a LuTx recipient who was successfully treated with mepolizumab for ABPA following LuTx. Prolonged administration of high dose prednisone was thus avoided. To our knowledge, this is the first case describing mepolizumab administration following LuTx. Mepolizumab seems particularly attractive as a corticosteroid-sparing agent or as an alternative option to antifungal treatments, because of its excellent safety profile and low risk of drug interactions.

Aspergillus-sensitized asthma in children.

BACKGROUND: Asthma is the most common chronic respiratory disease in childhood. Aspergillus fumigatus sensitivity may be involved in the pathogenesis of asthma by leading to different clinical presentations. OBJECTIVE: To investigate the demographic, clinical, laboratory, and radiological characteristics of A. fumigatus sensitivity in childhood asthma and identify associated risk factors and diagnostic parameters. METHODS: A total of 259 children with asthma were included in the study, 7 (2.7%) with allergic bronchopulmonary aspergillosis (ABPA), 84 (32.4%) with A. fumigatus-sensitized asthma (Af-SA), and 168 (64.9%) with A. fumigatus-unsensitized asthma (Af-UA). RESULTS: Aspergillus sensitivity was associated with early asthma onset and longer asthma duration. Total IgE level and asthma severity are highest in ABPA and higher in Af-SA. Absolute eosinophil count was higher, and FEV1 was lower in Af-SA and ABPA. Aspergillus fumigatus was associated with greater odds of being male (odds ratio [OR], 2.45), having atopic dermatitis (OR, 3.159), Alternaria sensitivity (OR, 10.37), and longer asthma duration (OR, 1.266). The best cut-off values for detecting A. fumigatus positivity were 363.5 IU/mL for total IgE and 455 cells/µL for absolute eosinophil count. In Af-SA compared to Af-UA, centrilobular nodules and peribronchial thickening were more common, and the bronchoarterial ratio was higher. CONCLUSIONS: Aspergillus sensitivity is a strong allergic stimulus in asthma, leading to laboratory, structural, clinical, and functional consequences. Af-SA is a distinct asthma endotype independent of ABPA that is characterized by increased risk of severe clinical presentations and impaired lung function.

Long-term use of omalizumab in patients with allergic bronchopulmonary aspergillosis: a tertiary-level care center experience.

INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease caused by a hypersensitivity reaction to antigens of Aspergillus fumigatus. OBJECTIVE: The aim of this study was to evaluate the long-term clinical outcomes of omalizumab use in patients with ABPA. METHODS: In this retrospective study, 12 patients diagnosed with ABPA and receiving omalizumab for at least 2 years, and 32 patients diagnosed with severe allergic asthma and receiving omalizumab for at least 2 years (control group) were evaluated. RESULTS: Evaluation was made of a total of 44 participants, comprising 11 (25%) males and 33 (75%) females, who received omalizumab for at least 2 years with the diagnosis of the control group (n = 32) and ABPA (n = 12). The increase in asthma control test (ACT) score after omalizumab was significant at 12 months and at 24 months in patients with ABPA. After omalizumab, the use of oral corticosteroid (OCS), the annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in patients with ABPA. The increase in forced expiratory volume in 1 s (FEV1) (%) and ACT score after omalizumab were significant at 12 months and at 24 months in the control group. After omalizumab, the use of OCS, annual number of asthma attacks and hospitalizations were significantly decreased at 12 months and at 24 months in the control group. CONCLUSION: Long-term omalizumab use in patients with ABPA seems to be an effective treatment for improving pulmonary function and reducing asthma exacerbations and hospitalizations.

ABPA and AFRS: addressing prevalence, early diagnosis, allergens, and occupational concerns.

OBJECTIVE: 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. DATA SOURCES: The data sources such as PubMed, Health and Safety Science Abstracts, OSH Update, Medline, and Google Scholar were searched. STUDY SELECTIONS: 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. RESULTS: 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. CONCLUSION: 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.

Efficacy of Biologics in Patients with Allergic Bronchopulmonary Aspergillosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively. METHODS: All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396. RESULTS: A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (- 2.29 [95%CI - 3.32, - 1.26]), OCS dosage (- 10.91 mg [95%CI - 18.98, - 2.85]), and total IgE levels (- 273.07 IU/mL [95%CI - 379.30, - 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment. CONCLUSION: These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings.

High attenuation mucus in bronchi with allergic bronchopulmonary mycosis.

BACKGROUND: High-attenuation mucus (HAM) is a specific manifestation of allergic bronchopulmonary mycosis (ABPM) on chest computed tomography (CT). OBJECTIVES: To compare the diagnostic accuracy of the two definitions of HAM and to clarify the clinical and radiographic characteristics of HAM-positive and HAM-negative ABPM. METHODS: CT images at the diagnosis of ABPM using Asano's criteria were retrospectively analysed. In Study #1, radiographic data obtained using the same CT apparatus in a single institute were analysed to determine the agreement between the two definitions of HAM: a mucus plug that is visually denser than the paraspinal muscles or that with a radiodensity ≥70 Hounsfield units. In Study #2, HAM was diagnosed by comparison with the paraspinal muscles in patients with ABPM reporting to 14 medical institutes in Japan. RESULTS: In Study #1, 93 mucus plugs from 26 patients were analysed. A substantial agreement for HAM diagnosis was observed between the two methods, with a κ coefficient of 0.72. In Study #2, 60 cases of ABPM were analysed; mucus plugs were present in all cases and HAM was diagnosed in 45 (75%) cases. The median A. fumigatus-specific IgE titre was significantly lower in HAM-positive patients than in HAM-negative patients (2.5 vs. 24.3 UA /mL, p = .004). Nodular shadows were observed more frequently in the airways distal to HAM than in those distal to non-HAM mucus plugs (59% vs. 32%, p < .001). CONCLUSION: In conclusion, agreement between the two methods to diagnose HAM was substantial. HAM was associated with some immunological and radiographic characteristics, including lower levels of sensitization to A. fumigatus and the presence of distal airway lesions.

Laboratory biomarkers in the diagnosis and follow-up of treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA), a severe inflammatory respiratory disease, is caused by a hypersensitivity reaction to the colonization of the airways with Aspergillus fumigatus. It is most often described in patients with asthma or cystic fibrosis. The diagnosis of ABPA is based on a combination of clinical, radiological, and immunological findings that have been included in different diagnostic criteria over the years. In this paper, we review the biomarkers included in these diagnostic criteria and novel research biomarkers that may be used in the diagnosis and treatment follow-up of ABPA in cystic fibrosis.

Allergic bronchopulmonary aspergillosis with atopic, nonatopic, and sans asthma-Factor analysis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence or absence of asthma, either atopic or nonatopic. We have tried to explore the essential components in the pathogenesis of the disease, which are either consistent and variable according to the presence and type of asthma. METHODS: Non-cystic fibrosis ABPA cases satisfying Asano's criteria were extracted from a prospective registry of ABPA and related diseases in Japan between 2013 and 2023. According to the type of preceding asthma, ABPA was classified into three groups: ABPA sans asthma (no preceding asthma), ABPA with atopic asthma, and ABPA with nonatopic asthma. Exploratory and confirmatory factor analyses were performed to identify the components that determined the clinical characteristics of ABPA. RESULTS: Among 106 cases of ABPA, 25 patients (24%) had ABPA sans asthma, whereas 57 (54%) and 24 (23%) had ABPA with atopic and nonatopic asthma, respectively. Factor analysis identified three components: allergic, eosinophilic, and fungal. Patients with atopic asthma showed the highest scores for the allergic component (p < .001), defined by total and allergen-specific IgE titers and lung opacities, and the lowest scores for the fungal component defined by the presence of specific precipitin/IgG or positive culture for A. fumigatus. Eosinophilic components, including peripheral blood eosinophil counts and presence of mucus plugs/high attenuation mucus in the bronchi, were consistent among the three groups. CONCLUSION: The eosinophilic component of ABPA is considered as the cardinal feature of ABPA regardless of the presence of preceding asthma or atopic predisposition.

The clinical significance of Aspergillus-positive respiratory samples.

BACKGROUND: Aspergilli moulds are frequently detected in sputum and other respiratory samples. It is not known what the significance of these findings is, or how to differentiate contamination, temporary or persistent colonisation from clinical infection when Aspergilli are found in respiratory samples. OBJECTIVES: In this study we studied the clinical significance of Aspergillus findings from respiratory samples. METHODS: We retrospectively evaluated 299 patients who had provided Aspergillus-positive respiratory samples in 2007-2016, which provided a follow-up time of 3-13 years. Data were collected from laboratory registry and Helsinki University Hospital medical records. Underlying diseases, immunosuppression, reasons for sample collection, clinical significance of positive Aspergillus culture, antifungal medication, and patient survival were assessed. RESULTS: Underlying pulmonary disease had 88% of patients, most commonly asthma (44%), bronchiectasis (30%) or COPD (21%). Corticosteroids (orally or inhalation therapy) prior to positive samples used 78%; the use of corticosteroids did not explain the development of Aspergillus disease. Pulmonary disease caused by Aspergillus was identified in 88 (29%) of the reviewed patients; remaining samples did not represent clinical disease. Chronic cavitary or fibrosing pulmonary aspergillosis (CCPA or CFPA) had 44 (49%) of the diseased. The probability of Aspergillus disease increased when Aspergillus-positive samples were given repeatedly within 1 year (p = .001). Mortality for all reasons was 45%. The repeated positive samples did not predict survival (p = .084), but the diagnosis of CPA did (p < .001). CONCLUSIONS: The possibility of Aspergillus disease increases when Aspergilli are found repeatedly, collection of samples should be repeated due to method insensitivity. Diagnosis of CPA predicted significantly lower survival.

Effectiveness and safety of omalizumab in patients with allergic bronchopulmonary aspergillosis with or without allergic rhinitis: a retrospective chart review.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Infection Dynamics of Aspergillus fumigatus in Adults with Cystic Fibrosis (CF).

OBJECTIVE: Aspergillus fumigatus (A. fumigatus) has emerged as a significant pathogen in patients with cystic fibrosis (CF) and currently is within the top five isolated organisms reported in several international CF patient registries. A. fumigatus has been attributed to disease progression, although its role remains controversial. There is a paucity of reports on its infection dynamics, it was the aim of this study to examine time to first laboratory reports of A. fumigatus acquisition and to correlate this with patient gender and cystic fibrosis transmembrane conductance regulator (CFTR) mutation type. METHODS: One hundred adult (≥ 18 years) CF patients were examined (50 females, 50 males; mean age 24.6 years ± 6.25 (SD), median age 24 years; maximum age 76 years). CFTR mutation groups consisted (i) F508del/F508del homozygous (n = 45), (ii) F508del/other heterozygous (n = 45) and (iii) others (n = 10). CFTR mutation type, patient gender, presence/absence of A. fumigatus and time (months) to first isolation of A. fumigatus were examined. RESULTS: Microbiological data was examined from 100 patients from birth to present (31/12/2021), equating to 2455 patient years. A. fumigatus was isolated from 66/100 (66%) adult CF patients; (i) F508del/F508del homozygous (82%; 37/45), (ii) F508del/other heterozygous (56%; 25/45) and (iii) others (40%; 4/10). Within the F508del/other heterozygous group, 14 mutations were noted on the second allele, with R560T and R117H collectively accounting for 36% of the second mutations. Four unique allele/allele mutations were noted in the Other Mutations category. There was a trend to a higher A. fumigatus acquisition in F508del/F508del homozygous patients than with F508del/other patients (p = 0.0529). Of the 66 patients who were positive for A. fumigatus, 35(53%) were male and 31(47%) were female. The median and mean time to first isolation of A. fumigatus in all A. fumigatus-positive patients was 119.5 months and 128 months, respectively, shortest time was 12 months, longest time 288 months. There was a statistical significance in time-to-first isolation in relation to CFTR mutation group (p = 0.0272), whereby F508del homozygous individuals had their first isolation of A. fumigatus at 116.8 ± 7.9 months (mean ± standard error of the mean (SEM)) and F508del heterozygous patients had their first isolate of A. fumigatus at 150.4 months ± 13.7 months (mean ± SEM), approximately 2.75 years after their F508del homozygous peers. There was no significant difference (p = 0.12) in time to first acquisiton between males and females, whereby males had their first A. fumigatus isolate at 118 ± 9.4 months, whereas females had their first A. fumigatus isolate at 140 ± 10.8 months. The highest rate of first A. fumigatus isolation was from 4 years until 16 years and by the age of 16 years, approximately 85% of A. fumigatus-positive patients had recorded their first A. fumigatus isolate. CONCLUSION: To minimise the risk of first acquisition of A. fumigatus, it is important that infection prevention educational messaging is delivered in the paediatric clinic, to enhance health literacy around A. fumigatus acquisition.

Fungal exposome, human health, and unmet needs: A 2022 update with special focus on allergy.

Humans inhale, ingest, and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom, reflected by its complex taxonomy, are in sharp contrast with our scarce knowledge about its distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health, through the lens of fungal allergy and other fungal hypersensitivity reactions. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal-related hypersensitivity diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.

Clinical characteristics of allergic bronchopulmonary aspergillosis in patients with and without bronchiectasis.

OBJECTIVE: Allergic bronchopulmonary aspergillosis (ABPA) is classified radiologically as serologic ABPA (ABPA-S) or ABPA with central bronchiectasis (ABPA-CB). This retrospective case series study aimed to describe and compare the clinical characteristics of both forms of ABPA. METHODS: Patients with ABPA treated in the hospital between February 2011 and June 2019 were enrolled and were divided into ABPA-S and ABPA-CB groups based on whether their cases were complicated with central bronchiectasis. Demographic data, symptoms, laboratory values, comorbidities, and image findings were collected. ABPA-S patients were followed up retrospectively through medical records. RESULTS: Ninety-three (93) patients were enrolled, including 74 ABPA-CB patients and 19 ABPA-S patients. The most common predisposing condition was asthma (36.6%), with a median course of 30 years (IQR 13-42.5) prior to ABPA diagnosis. Patients of 54.8% had been misdiagnosed, with ABPA-S more likely than ABPA-CB to have been misdiagnosed as asthma (p < 0.01). Obstructive ventilation dysfunction and mixed ventilation dysfunction were found in 21 patients (22.6%) and 16 patients (17.2%), respectively. Compared with ABPA-S, ABPA-CB had a higher median blood eosinophil count (880 vs. 700 cells/µl), serum IgE (2957 vs. 2616 IU/ml), and Aspergillus fumigatus specific-IgE (20.6 vs. 7.31 kUA/L), although these findings were not statistically significant. Three ABPA-S patients developed bronchiectasis during follow-up and experienced relapses more than twice. CONCLUSIONS: Our findings suggested that the clinical characteristics between ABPA-CB and ABPA-S were mostly similar. ABPA-S had a relatively lower immunological activity level than ABPA-CB but was still immunologically active and could develop bronchiectasis.

Dupilumab: A Review of Present Indications and Off-Label Uses.

Recent advances in our understanding of T2 inflammation have revealed more diseases in which T2 inflammation is involved. Dupilumab is a recently developed monoclonal antibody that blocks signaling of IL-4 and IL-13, both of which are crucial cytokines in the T2 response. New possible indications are increasingly explored and include skin diseases, such as prurigo nodularis, nummular eczema, allergic contact dermatitis, chronic hand eczema, spontaneous chronic urticaria, bullous pemphigoid, alopecia areata, and Netherton syndrome, as well as respiratory diseases, such as allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, and allergic rhinitis. In addition, eosinophilic gastrointestinal disorders, particularly eosinophilic esophagitis, and food allergy, are also research fields of interest. Here, we review published data and clinical trials examining the use of dupilumab in these disorders.

New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation.

BACKGROUND: There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic bronchopulmonary mycosis (ABPM) are currently available. OBJECTIVE: This study proposes new diagnostic criteria for ABPA/ABPM, consisting of 10 components, and compares its sensitivity and specificity to existing methods. METHODS: Rosenberg-Patterson criteria proposed in 1977, the International Society for Human and Animal Mycology (ISHAM) criteria proposed in 2013, and this new criteria were applied to 79 cases with pathological ABPM and the control population with allergic mucin in the absence of fungal hyphae (n = 37), chronic eosinophilic pneumonia (n = 64), Aspergillus-sensitized severe asthma (n = 26), or chronic pulmonary aspergillosis (n = 24). These criteria were also applied to the 179 cases with physician-diagnosed ABPA/ABPM in a nationwide Japanese survey. RESULTS: The sensitivity for pathological ABPM with Rosenberg-Patterson criteria, ISHAM criteria, and this new criteria were 25.3%, 77.2%, and 96.2%, respectively. The sensitivity for physician-diagnosed ABPA/ABPM were 49.2%, 82.7%, and 94.4%, respectively. The areas under the curve for the receiver-operating characteristic curves were 0.85, 0.90, and 0.98, respectively. The sensitivity for ABPM cases that were culture-positive for non-Aspergillus fungi were 13.0%, 47.8%, and 91.3%, respectively. CONCLUSIONS: The new diagnostic criteria, compared with existing criteria, showed better sensitivity and specificity for diagnosing ABPA/ABPM.

Fungal asthma among Ugandan adult asthmatics.

Fungal sensitization is associated with poor asthma control. We aimed to determine the prevalence and factors associated with fungal asthma among Ugandan adults. Individuals aged ≥18 years with a new diagnosis of asthma in the last 12 months participating in the African Severe Asthma Program constituted the study population. Skin prick test results, clinical and demographic data were retrieved from the database, and serum Aspergillus fumigatus specific antibodies and total IgE were measured in stored blood. We enrolled 374 patients, median (IQR) age 34 (25-45) years, 286 (76.5%) females and 286 (76.5%) with severe asthma. Prevalence of Aspergillus fumigatus sensitization was 42.0% (95% CI: 37.1-47.0%), allergic bronchopulmonary aspergillosis (ABPA) 3.2% (1.8-5.5%), severe asthma with fungal sensitization (SAFS) 16% (12.7-20.1%) and allergic bronchopulmonary mycosis (ABPM) 2.9% (1.7-5.2%). Older age (55-64 years) (crude odds ratio (cOR) = 2.6), sensitization to at least one allergen (cOR = 9.38) and hypertension (cOR = 1.99) were significantly associated with Aspergillus sensitization, whereas tertiary education level (cOR = 0.29), severe depression (cOR = 0.15) and strong emotions (cOR = 0.47) were not. High occupational exposure to Aspergillus (cOR = 4.26) and contact with moulds (cOR = 14.28) were significantly associated with ABPA. Palpitations (cOR = 5.54), uncontrolled asthma (cOR = 3.54), eczema/dermatitis (cOR = 3.07), poor lung function (cOR = 2.11) and frequent exacerbations (cOR = 1.01) were significantly associated with SAFS. Eczema/dermatitis (cOR = 1.55) was significantly associated with ABPM, but cold weather trigger (cOR = 0.24) was not. Fungal asthma is a significant problem among Ugandans with asthma and should be particularly considered in individuals who remain uncontrolled despite optimal standard of care for asthma, as it is responsive to available and affordable oral antifungal therapy. LAY SUMMARY: This study showed that fungal asthma is a significant problem among Ugandans with asthma with a high prevalence. Fungal asthma should be considered in patients with uncontrolled asthma despite receiving optimal standard of care. This is the first modern attempt to define these endotypes of asthma in Africa.

Diagnosis of allergic bronchopulmonary aspergillosis in patients with persistent allergic asthma using three different diagnostic algorithms.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) has been reported in various degrees among patients with persistent allergic asthma (PAA). Currently, there is no gold standard approach for diagnosis of ABPA. OBJECTIVES: In the current study, we aimed the evaluation of three different mainly used algorithms as Rosenberg & Patterson (A), ISHAM Working Group (B) and Greenberger (C) for diagnosis of ABPA in 200 patients with underlying PAA. METHODS: All patients were evaluated using Aspergillus skin prick test (SPTAf), Aspergillus-specific IgE (sIgEAf) and IgG (sIgGAf), total IgE (tIgE), pulmonary function tests, radiological findings and peripheral blood eosinophil count. The prevalence rate of ABPA in PAA patients was estimated by three diagnostic criteria. We used Latent Class Analysis for the evaluation of different diagnostic parameters in different applied ABPA diagnostic algorithms. RESULTS: Aspergillus sensitisation was observed in 30 (15.0%) patients. According to algorithms A, B and C, nine (4.5%), six (3.0%) and 11 (5.5%) of patients were diagnosed with ABPA, respectively. The sensitivity and specificity of criteria B and C were (55.6% and 99.5%) and (100.0% and 98.9%) respectively. sIgEAf and sIgGAf showed the high significant sensitivity. The performance of algorithm A, in terms of sensitivity and specificity, was somewhat better than algorithm B. CONCLUSION: Our study demonstrated that the sensitivity of different diagnostic algorithms could change the prevalence rate of ABPA. We also found that all of three criteria resulted an adequate specificity for ABPA diagnosis. A consensus patterns combining elements of all three criteria may warrant a better diagnostic algorithm.

Total unilateral pulmonary collapse secondary to allergic bronchopulmonary aspergillosis: a case series of an unusual cause of complete atelectasis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a bronchopulmonary disease caused by a complex hypersensitivity to Aspergillus and is usually associated with underlying respiratory diseases such as asthma or cystic fibrosis. Mucus plugging can lead to segmental or lobar atelectasis, but complete lung atelectasis has been exceptionally reported in the literature, making it difficult to diagnose. The diagnosis of ABPA may however be suggested in patients without known predisposing respiratory disorder, even in the absence of other relevant radiographic findings. CASE PRESENTATION: We report five cases of total unilateral lung collapse secondary to ABPA in 70-81-year-old women. Two of them had a past history of ABPA, while total unilateral lung collapse was the first sign of the disease in the other three patients, contributing to the initial misdiagnosis. Flexible bronchoscopy was initially performed to remove mucus plugs from the obstructed airways but was inefficient in four cases. Corticosteroid and/or antifungal treatment was needed. CONCLUSION: ABPA can cause total unilateral lung collapse even in patients without known underlying chronic respiratory disease, making the diagnosis difficult. Flexible bronchoscopy should be considered when lung collapse is associated with respiratory distress but corticosteroids are the mainstay treatment for ABPA.

Proteomic Analysis of Serum Differentially Expressed Proteins Between Allergic Bronchopulmonary Aspergillosis and Asthma.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) constantly develops in asthmatics, which has not been fully investigated. OBJECTIVES: This study aimed to investigate serum differentially expressed proteins (DEPs) between ABPA and asthma using the new approach isobaric tags by relative and absolute quantitation (iTRAQ). METHODS: Each 16 serum samples from ABPA or asthmatic subjects were pooled and screened using iTRAQ. After bioinformatic analysis, five candidate DEPs were validated in the enlarged serum samples from additional 21 ABPA, 31 asthmatic and 20 healthy subjects using ELISA. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic power of carnosine dipeptidase 1 (CNDP1). RESULTS: A total of 29 DEPs were screened out between ABPA and asthmatic groups. Over half of them were enriched in proteolysis and regulation of protein metabolic process. Further verification showed serum levels of immunoglobulin heavy constant gamma 1, α-1-acid glycoprotein 1, corticosteroid-binding globulin and vitronectin were neither differentially altered between ABPA and asthma nor consistent with the proteomic analysis. Only serum CNDP1 was significantly decreased in ABPA patients, compared with asthmatics and healthy controls (P < 0.01 and P < 0.05). The ROC analysis determined 10.73 ng/mL as the cutoff value of CNDP1, which could distinguish ABPA among asthmatics (AUC 0.770, 95%CI 0.632-0.875, P < 0.001). CONCLUSIONS: This study firstly identified serological DEPs between ABPA and asthma using the new technique iTRAQ. Serum CNDP1 might assist the differential diagnosis of ABPA from asthma and serve as a new pathogenetic factor in fungal colonization and sensitization.