Fractional exhaled nitric oxide, a potential biomarker for evaluating glucocorticoids treatment and prognosis in allergic bronchopulmonary aspergillosis.
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
BACKGROUND:Allergic bronchopulmonary aspergillosis (ABPA) is characterized by enhanced T2 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 T2 inflammation. However, the clinical significance of FeNO in ABPA remains unclear. OBJECTIVE: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. METHODS: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. RESULTS: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. CONCLUSION: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.
10.1016/j.anai.2024.05.010
Comparison of diagnostic efficiency of detecting IgG and IgE with immunoassay method in diagnosing ABPA: a meta-analysis.
BMC pulmonary medicine
BACKGROUND:Hitherto, the bulk of diagnostic criteria regards Aspergillus-specific immunoglobulin E as a key item, and regard IgG as an auxiliary method in diagnose. Nevertheless, there is no conclusive study in summarize the performance of IgG and IgE diagnosing ABPA. METHODS:We conducted a systematic review to identify studies report results of IgE and IgG detection in diagnosing ABPA. QUADAS-2 tool was used to evaluate included studies, and we applied the HSROC model to calculate the pooled sensitivity and specificity. Deeks' funnel was derived to evaluated the public bias of included studies, and Cochrane Q test and I statistic were used to test the heterogeneity. RESULTS:Eleven studies were included in this study (1127 subjects and 215 for IgE and IgG). Deeks's test for IgE and IgG were 0.10 and 0.19. The pooled sensitivity and specificity for IgE were 0.83 (95%CI: 0.77, 0.90) and 0.89 (0.83, 0.94), and for IgG were 0.93 (0.87, 0.97) and 0.73 (0.62,0.82), with P value < 0.001. The PLR and NLR for IgE were 7.80 (5.03,12.10) and 0.19 (0.13,0.27), while for IgG were 3.45 (2.40,4.96) and 0.09 (0.05,0.17). The combined diagnostic odds ratio and diagnostic score were 41.49 (26.74,64.36) and3.73 (3.29,4.16) for IgE, respectively, and were 38.42 (19.23,76.79) and 3.65 (2.96,4.34) for IgG. CONCLUSION:The sensitivity for IgG diagnosing ABPA is higher than IgE, while the specificity for IgE is higher. IgG might be able to play a more important role in filtering ABPA patients.
10.1186/s12890-023-02620-3
Diagnosis of allergic bronchopulmonary aspergillosis in patients with persistent allergic asthma using three different diagnostic algorithms.
Mycoses
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.
10.1111/myc.13217
Which Are the Optimal Criteria for the Diagnosis of Allergic Bronchopulmonary Aspergillosis? A Latent Class Analysis.
The journal of allergy and clinical immunology. In practice
BACKGROUND:The ideal criteria for diagnosing allergic bronchopulmonary aspergillosis (ABPA) remain unknown because of the lack of a criterion standard. Latent class analysis using a probabilistic modeling technique can circumvent the need for a reference standard. OBJECTIVE:To compare the diagnostic performance of various criteria used for evaluating ABPA. METHODS:We prospectively enrolled consecutive cases of bronchial asthma and performed a series of investigations used for the diagnosis of ABPA. We used latent class analysis to analyze the performance of various existing and novel diagnostic criteria. RESULTS:Of the 543 subjects (mean age, 37 years; 319 women), 338 (62.2%) and 205 (37.8%) were labeled as "mild-to-moderate" and "severe" asthma cases, respectively. The subjects with severe asthma had a longer duration of asthma and a higher number of exacerbations in the previous year. The prevalence of Aspergillus fumigatus sensitization was 41% and 30%, using the A fumigatus-specific IgE and skin test, respectively. The prevalence of ABPA was 16%, using both the Rosenberg-Patterson and the International Society for Human and Animal Mycology (ISHAM)-ABPA Working Group criteria. The ISHAM criteria were slightly more sensitive (89% vs 81%) and specific (99% vs 98%) than the Patterson criteria. We obtained optimal diagnostic performance by altering the existing ISHAM criteria (serum total IgE >500 international units/mL, excluding the skin test, and using computed tomography of thorax instead of chest radiograph). CONCLUSIONS:The ISHAM-ABPA Working Group criteria were only marginally better than the Patterson criteria in diagnosing ABPA among patients with asthma younger than 66 years. The diagnostic performance however improved by modifying the prevailing ISHAM criteria, but with increased cost.
10.1016/j.jaip.2020.08.043
A randomised trial of prednisolone prednisolone and itraconazole in acute-stage allergic bronchopulmonary aspergillosis complicating asthma.
The European respiratory journal
BACKGROUND:Whether a combination of glucocorticoid and antifungal triazole is superior to glucocorticoid alone in reducing exacerbations in patients with allergic bronchopulmonary aspergillosis (ABPA) remains unknown. We aimed to compare the efficacy and safety of prednisolone-itraconazole combination prednisolone monotherapy in ABPA. METHODS:We randomised subjects with treatment-naïve acute-stage ABPA complicating asthma to receive either prednisolone alone (4 months) or a combination of prednisolone and itraconazole (4 and 6 months, respectively). The primary outcomes were exacerbation rates at 12 months and glucocorticoid-dependent ABPA within 24 months of initiating treatment. The key secondary outcomes were response rates, percentage decline in serum total IgE at 6 weeks, time to first ABPA exacerbation and treatment-emergent adverse events (TEAEs). RESULTS:We randomised 191 subjects to receive either prednisolone (n=94) or prednisolone-itraconazole combination (n=97). The 1-year exacerbation rate was 33% and 20.6% in the prednisolone monotherapy and prednisolone-itraconazole combination arms, respectively (p=0.054). None of the participants progressed to glucocorticoid-dependent ABPA. All of the subjects experienced a composite response at 6 weeks, along with a decline in serum total IgE (mean decline 47.6% 45.5%). The mean time to first ABPA exacerbation (417 days) was not different between the groups. None of the participants required modification of therapy due to TEAEs. CONCLUSIONS:There was a trend towards a decline in ABPA exacerbations at 1 year with the prednisolone-itraconazole combination prednisolone monotherapy. A three-arm trial comparing itraconazole and prednisolone monotherapies with their combination, preferably in a multicentric design, is required to define the best treatment strategy for acute-stage ABPA.
10.1183/13993003.01787-2021
Prevalence of Aspergillus Sensitization and Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma: A Systematic Review of Global Data.
The journal of allergy and clinical immunology. In practice
BACKGROUND:The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients remains unclear and is likely different across geographic locales. OBJECTIVE:To systematically review the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in adults with bronchial asthma. METHODS:We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in at least 50 asthmatic subjects. The primary outcome was to assess the prevalence of ABPA. The secondary outcome was to evaluate the prevalence of AS in asthma and that of ABPA in asthma with AS. We pooled the prevalence estimates using a random-effects model and examined the factors influencing the prevalence using multivariate meta-regression. RESULTS:Of the 11,801 records retrieved, 86 studies with 25,770 asthmatic subjects met the inclusion criteria. Most of the studies were from tertiary care centers. The pooled prevalence of ABPA in asthma (47 studies; 9822 asthmatic subjects) was 11.3% (95% CI, 8.7-14.2). The pooled prevalence of AS in asthma (73 studies; 23,003 asthmatic subjects) was 25.1% (95% CI, 20.5-30.0), whereas the prevalence of ABPA in AS (36 studies; 2954 asthmatic subjects) was 37.0% (95% CI, 27.9-46.6). Multivariate meta-regression identified studies published from India (odds ratio, 1.11; 95% CI, 1.01-1.23) as the only factor associated with higher ABPA prevalence. There was presence of significant statistical heterogeneity and publication bias. CONCLUSIONS:We found a high prevalence of ABPA in adult asthmatic subjects, underscoring the need for screening for ABPA in all asthmatic subjects seeking tertiary care.
10.1016/j.jaip.2023.04.009
Clinician variability in the diagnosis and treatment of aspergillus fumigatus-related conditions in cystic fibrosis: An international survey.
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
BACKGROUND:The diagnosis and treatment of Aspergillus fumigatus (Af)-related conditions remain a challenge in cystic fibrosis (CF) due to overlapping features of disease and absence of clinical guidelines for Af-related conditions outside of ABPA. OBJECTIVE:To investigate the differences of clinical practice in the diagnosis and management of Af-related conditions in CF. METHODS:We conducted an international survey to CF clinicians to ascertain the screening, diagnostic, and treatment practices for Af-related conditions in CF. Respondents were grouped into geographical regions and regional comparisons using chi-square tests of independence or Fisher's tests were performed. RESULTS:A total of 319 survey responses from 35 countries were analyzed. We observed differences in use and frequency of fungus culture, Aspergillus-specific IgE and IgG, skin prick testing, and pulmonary function testing as screening for Af-related conditions between the geographical regions. ABPA and Aspergillus bronchitis diagnostic criteria selection differed by region; significantly greater proportion of United States (US) and Canadian clinicians were unable to define Aspergillus bronchitis compared to Europe and other regions. Decision to treat ABPA was uniform across regions, but the consideration of Aspergillus bronchitis as a clinical disease warranting therapy differed between regions. The use of glucocorticoid and itraconazole was the first-line treatment of ABPA among clinicians; however, prednisone monotherapy was more common in US and Canada. CONCLUSIONS:Significant variability in the diagnosis and management of Aspergillus-related conditions in CF was observed. Future studies are necessary to better harmonize the approach to Af-related disease in CF.
10.1016/j.jcf.2021.07.008
Laboratory biomarkers in the diagnosis and follow-up of treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis.
Critical reviews in clinical laboratory sciences
Allergic bronchopulmonary aspergillosis (ABPA), a severe inflammatory respiratory disease, is caused by a hypersensitivity reaction to the colonization of the airways with . 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.
10.1080/10408363.2022.2101612
[Development in diagnostic criteria for allergic bronchopulmonary aspergillosis].
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung disease caused by the sensitization of . In recent years, the research into ABPA has progressed, the testing methods have improved and the diagnostic criteria have been continuously updated. There is no gold standard for the diagnosis of the disease. The diagnostic criteria for ABPA include predisposing diseases, fungal-related immunoassay and pathological examination. Understanding the clinical significance of ABPA diagnostic criteria may help to prevent irreversible bronchopulmonary injury, improve respiratory function and improve the prognosis of patients.
10.3760/cma.j.cn112147-20221124-00925
Prospective Evaluation of -Specific IgG in Patients With Cystic Fibrosis.
Eschenhagen Patience,Grehn Claudia,Schwarz Carsten
Frontiers in cellular and infection microbiology
Background:In Cystic Fibrosis (CF), the airways are often colonized by opportunistic fungi. The most frequently detected mold is (). diseases are associated with significant morbidity and mortality. The most common clinical picture caused by is allergic bronchopulmonary aspergillosis (ABPA), triggered by an immunological reaction against . bronchitis and invasive aspergillosis rarely occur in CF as a result of spore colonization and germination. Since pulmonary mycoses and exacerbations by other pathogens overlap in clinical, radiological, and immunological characteristics, diagnosis still remains a challenge. The search for reliable, widely available biomarkers for diseases is therefore still an important task today. Objectives:specific IgG m3 is broadly available. Sensitivity and specificity data are contradictory and differ depending on the study population. In our prospective study on pulmonary diseases in CF, we determined specific IgG m3 in order to test its suitability as a biomarker for acute diseases and as a follow-up parameter. Methods:In this prospective single center study, 109 patients with CF were screened from 2016 to 2019 for -associated diseases. According to diagnostic criteria, they were divided into four groups (control, bronchitis, ABPA, pneumonia). The groups were compared with respect to the level of -specific IgG (ImmunoCAP Gm3). We performed a receiver operating characteristic (ROC) curve analysis to determine cut-off, sensitivity and specificity. Twenty-one patients could be enrolled for a follow-up examination. Results:Of the 109 patients, 36 were classified as acute -disease ( bronchitis, ABPA, pneumonia). Of these, 21 patients completed follow up-screening. The median -specific Gm3 was higher in the acute -disease groups. There was a significant difference in -specific IgG m3 compared to the control group without acute -disease. Overall, there was a large interindividual distribution of Gm3. A cut-off value of 78.05 mg/L for Gm3 was calculated to discriminate controls and patients with ABPA/pneumonia with a specificity of 75% and a sensitivity of 74.6%. The follow up examination of 21 patients showed a decrease of Gm3 in most patients without statistical significance due to the small number of follow up patients. Conclusion:specific IgG may be a useful biomarker for acute ABPA and pneumonia, but not for bronchitis in CF. However, due to the large interindividual variability of Gm3, it should only be interpreted alongside other biomarkers. Therefore, due to its broad availability, it could be suitable as a biomarker for ABPA and pneumonia in CF, if the results can be supported by a larger multicenter cohort.
10.3389/fcimb.2020.602836
Clinical Characteristics and Prognosis of Allergic Bronchopulmonary Aspergillosis: A Retrospective Cohort Study.
Journal of asthma and allergy
BACKGROUND:The clinical features, treatment, and prognosis of allergic bronchopulmonary aspergillosis (ABPA) are not well-defined. OBJECTIVE:We aimed to investigate the clinical characteristics, therapy, and prognosis of ABPA to aid its clinical recognition. METHODS:A total of 232 patients with ABPA were analyzed retrospectively. The characteristics of ABPA in terms of its misdiagnosis, computed tomography classification, therapy, and its relationship with asthma were analyzed, and risk factors for acute exacerbation of ABPA were analyzed based on follow-up data. RESULTS:Of the 232 ABPA patients, 132 had a history of misdiagnosis. Compared with the misdiagnosed patients, ABPA patients with central bronchiectasis, a high total eosinophil count, and mucus plugs were less likely to be misdiagnosed. Compared with serological ABPA, ABPA with central bronchiectasis was more likely to occur in older people and in patients with mucus plugs, and decreased forced vital capacity and diffusing capacity for carbon monoxide. ABPA patients with asthma were more likely to have bronchiectasis, decreased lung function in 1 s FEV1 and FEV1/FVC, and shorter time to first acute exacerbation compared with ABPA patients without asthma. Patients receiving glucocorticoids plus antifungal therapy had a longer time to first exacerbation than those receiving glucocorticoid therapy alone. Univariate and multivariate analyses revealed that duration of asthma history, duration of misdiagnosis, mucus plugs, and poor pulmonary function were risk factors for acute exacerbation of ABPA. CONCLUSION:To our knowledge, this is the largest sample size study of ABPA in China. ABPA patients with a history of asthma and/or central bronchiectasis on high-resolution computed tomography are prone to frequent acute exacerbations. The use of glucocorticoids combined with antifungal drugs can prolong the time to the first acute exacerbation in ABPA patients. Longer durations of asthma history and misdiagnosis, mucus plugs, and poor pulmonary function are risk factors for acute exacerbation of ABPA.
10.2147/JAA.S345427
Clinical and immunological characteristics of -sensitized asthma and allergic bronchopulmonary aspergillosis.
Frontiers in immunology
Background: () is a common airborne allergen that contributes to allergic asthma. In some patients, can colonize in the airway and lead to allergic bronchopulmonary aspergillosis (ABPA). However, our understanding of the pathogenesis of -sensitized asthma and ABPA remains inadequate. Objective:We aimed to investigate the clinical and immunological characteristics of -sensitized asthma and ABPA. Methods:A total of 64 ABPA and 57 A-sensitized asthma patients were enrolled in the study, and 33 non--sensitized asthma patients served as the control group. The clinical and immunological parameters included lung function, fractional exhaled nitric oxide (FeNO), induced sputum and blood cell analysis, specific IgE/IgG/IgA of A.f and its components, cytokines (IL-33, IL-25, and TSLP) and CD4T cell subsets. Results:The eosinophils in blood, induced sputum, and FeNO were significantly higher in ABPA patients compared to that in -sensitized patients. The combination of FeNO and eosinophils (EO) parameters presented good diagnostic efficiency in differentiating (+) asthma from ABPA, with a sensitivity of 80% and a specificity of 100%. Specific IgE, IgG, and IgA against also increased in ABPA patients. However, serum IL-25, IL-33, and TSLP showed no significant differences between the two groups. Cell analysis showed an increase in IFN-γTh1 cells in the ABPA patients. FlowSOM analysis further confirmed that the frequency of CD3CD4PD-1CD127IFN-γT cells was higher in ABPA patients. Conclusion:Our findings suggest the distinct humoral and cell immunological responses in -sensitized asthma and ABPA patients. ABPA patients have more severe eosinophilic inflammation and enhanced Th1 responses compared with -sensitized asthma patients.
10.3389/fimmu.2022.939127
Relationship between Aspergillus and asthma.
Allergology international : official journal of the Japanese Society of Allergology
Fungal sensitization is highly prevalent in severe asthma. The relationship between fungus and asthma, especially Aspergillus fumigatus, has been the subject of extensive research. The ubiquitous presence of A. fumigatus, its thermotolerant nature, the respirable size of its conidia, and its ability to produce potent allergens are pivotal in worsening asthma control. Due to the diverse clinical manifestations of fungal asthma and the lack of specific biomarkers, its diagnosis remains intricate. Diagnosing fungal asthma requires carefully assessing the patient's clinical history, immunological tests, and imaging. Depending on the severity, patients with fungal asthma require personalized treatment plans, including inhaled corticosteroids and bronchodilators, and antifungal therapy. This review provides a comprehensive overview of the association between Aspergillus and asthma by reviewing the relevant literature and highlighting key findings. We discuss the diagnosis of various entities included in fungal asthma. We also debate whether newer definitions, including allergic fungal airway disease, offer any additional advantages over the existing ones. Finally, we provide the current treatment options for the individual entities, including A. fumigatus-associated asthma, severe asthma with fungal sensitization, and allergic bronchopulmonary mycoses.
10.1016/j.alit.2023.08.004
Allergic Bronchopulmonary Aspergillosis.
Clinics in chest medicine
Allergic bronchopulmonary aspergillosis (ABPA) is a complex allergic disorder caused by immune reactions against Aspergillus fumigatus. ABPA most commonly complicates the course of patients with poorly controlled asthma. Patients commonly present with uncontrolled asthma, fleeting pulmonary opacities, and bronchiectasis. Pathogenetically, ABPA is characterized by the persistence of A. fumigatus in the airways and an exaggerated type-2 immune response. The interest in ABPA stems from the fact that bronchiectasis in ABPA can be prevented if the disorder is diagnosed timely and treated appropriately. Herein, we summarize the current concepts in the epidemiology, pathogenesis, diagnosis, and treatment of ABPA.
10.1016/j.ccm.2021.12.002
Case Report: Allergic Bronchopulmonary Aspergillosis Revealing Asthma.
Snen Houda,Kallel Aicha,Blibech Hana,Jemel Sana,Salah Nozha Ben,Marouen Sonia,Mehiri Nadia,Belhaj Slah,Louzir Bechir,Kallel Kalthoum
Frontiers in immunology
Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to which colonizes the airways of patients with asthma and cystic fibrosis. Its diagnosis could be difficult in some cases due to atypical presentations especially when there is no medical history of asthma. Treatment of ABPA is frequently associated to side effects but cumulated drug toxicity due to different molecules is rarely reported. An accurate choice among the different available molecules and effective on ABPA is crucial. We report a case of ABPA in a woman without a known history of asthma. She presented an acute bronchitis with wheezing dyspnea leading to an acute respiratory failure. She was hospitalized in the intensive care unit. The bronchoscopy revealed a complete obstruction of the left primary bronchus by a sticky greenish material. The culture of this material isolated and that of bronchial aspiration fluid isolated . The diagnosis of ABPA was based on elevated eosinophil count, the presence of specific IgE and IgG against and left segmental collapse on chest computed tomography. The patient received an inhaled treatment for her asthma and a high dose of oral corticosteroids for ABPA. Her symptoms improved but during the decrease of corticosteroids, the patient presented a relapse. She received itraconazole in addition to corticosteroids. Four months later, she presented a drug-induced hepatitis due to itraconazole which was immediately stopped. During the monitoring of her asthma which was partially controlled, the patient presented an aseptic osteonecrosis of both femoral heads that required surgery. Nine months after itraconazole discontinuation, she presented a second relapse of her ABPA. She received voriconazole for nine months associated with a low dose of systemic corticosteroid therapy with an improvement of her symptoms. After discontinuation of antifungal treatment, there was no relapse for one year follow-up.
10.3389/fimmu.2021.695954
Epidemiology and outcomes of allergic bronchopulmonary aspergillosis in the elderly.
Muthu Valliappan,Sehgal Inderpaul Singh,Prasad Kuruswamy Thurai,Dhooria Sahajal,Garg Mandeep,Aggarwal Ashutosh N,Chakrabarti Arunaloke,Agarwal Ritesh
Mycoses
BACKGROUND:The prevalence and outcomes of allergic bronchopulmonary aspergillosis (ABPA) in the elderly remain unknown. METHODS:We reviewed our database to identify the proportion of subjects diagnosed with ABPA at ≥60 years of age (ABPA-elderly). We compared the clinical features, treatment and outcomes of ABPA-elderly versus the non-elderly (ABPA diagnosed at <60 years of age). RESULTS:Between 2007 and 2019, we encountered 810 ABPA subjects with a mean age of 34.9 years (49.4% women). Of these, 43 (5.3%) were aged ≥60 years (ABPA-elderly). There was a trend towards lower median (interquartile range [IQR]) serum total IgE (4900 [2659-10000] vs. 7156 [23360-11963] IU/mL; P = .06) and Aspergillus fumigatus-specific IgE (12.3 [4.8-29.6] vs. 22.4 [7.7-41.5] kUA/L; P = .06) in the elderly than the non-elderly. Eosinophil counts were similar in the two groups. The median [IQR] number of segments involved by bronchiectasis (5 [2-9] vs. 7 [4-11]) was significantly lower in the ABPA-elderly (P = .001). The proportion of subjects experiencing ABPA exacerbations was significantly (P = .047) lower in the elderly (25.6%) vs. the non-elderly (40.8%). There was also a tendency towards a lower mean number of exacerbations in the elderly (155 vs. 208 exacerbation per 1000 person-years) than the non-elderly (P = .09). There was also a trend towards longer mean time to first exacerbation in the ABPA-elderly than the non-elderly (1612 vs. 1159 days). CONCLUSION:ABPA was uncommon in the elderly. The bronchiectasis is less extensive with a trend towards lower immunological severity and fewer exacerbations in the elderly than the non-elderly subjects with ABPA.
10.1111/myc.13388
High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap.
Tiew Pei Yee,Lim Albert Yick Hou,Keir Holly R,Dicker Alison J,Mac Aogáin Micheál,Pang Sze Lei,Low Teck Boon,Hassan Tidi Maharani,Poh Mau Ern,Xu Huiying,Ong Thun How,Koh Mariko Siyue,Abisheganaden John Arputhan,Tee Augustine,Chew Fook Tim,Chalmers James D,Chotirmall Sanjay H
Chest
BACKGROUND:Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION:What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap? STUDY DESIGN:Prospective, observational, cross-sectional study. METHODS:We prospectively recruited 280 patients during periods of clinical stability with bronchiectasis (n = 183), COPD (n = 50), and BCO (n = 47) from six hospitals across three countries (Singapore, Malaysia, and Scotland). We assessed sensitization responses (as specific IgE) to a panel of recombinant Aspergillus fumigatus allergens and the occurrence of ABPA in relationship to clinical outcomes. RESULTS:Individuals with BCO show an increased frequency and clinical severity of ABPA compared with those with COPD and bronchiectasis without overlap. BCO-associated ABPA is associated with more severe disease, higher exacerbation rates, and lower lung function when compared with ABPA occurring in the absence of overlap. BCO with a severe bronchiectasis severity index (BSI; > 9) is associated significantly with the occurrence of ABPA that is unrelated to underlying COPD severity. CONCLUSIONS:BCO demonstrates a high frequency of ABPA that is associated with a severe BSI (> 9) and poor clinical outcomes. Clinicians should maintain a high index of suspicion for the potential development of ABPA in patients with BCO with high BSI.
10.1016/j.chest.2021.07.2165
Biologic drugs in treating allergic bronchopulmonary aspergillosis in patients with cystic fibrosis: a systematic review.
European respiratory review : an official journal of the European Respiratory Society
BACKGROUND: is a common saprophytic fungus causing allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (CF). The recommended first-line treatment for ABPA is oral steroids, followed by antifungal therapy. However, both treatments are not free from adverse effects; thus, efforts are being made to identify new drugs showing the same effectiveness but with fewer or no side-effects. Therein, biologic drugs have been significantly implemented in clinical practice in treating ABPA in patients with CF. OBJECTIVE:To systematically review the available literature, providing evidence for the administration of biologic drugs as a new potential treatment of ABPA in both the paediatric and adult populations with CF. METHODS:A systematic review of the literature published between January 2007 and July 2021 was performed, using a protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42021270932). RESULTS:A total of 21 studies focusing on the use of biologics in treating ABPA in CF patients was included. We highlighted a paucity of data providing evidence for biologic drug use in ABPA. CONCLUSION:Scientific evidence is insufficient to support firm conclusions and randomised clinical trials are urgently required to investigate the efficacy and safety of biologics for ABPA in CF patients.
10.1183/16000617.0011-2022
Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
The Cochrane database of systematic reviews
BACKGROUND:Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. OBJECTIVES:The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy. SEARCH METHODS:We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials. SELECTION CRITERIA:Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS:The searches identified six trials; none of which met the inclusion criteria for the review. MAIN RESULTS:We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update. AUTHORS' CONCLUSIONS:At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.
10.1002/14651858.CD002204.pub5
[A PATIENT WITH ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS (ABPA) WHO HAD UNDERGONE TUBERCULOSIS TREATMENT TWICE].
Mizuhashi Keiichi,Fujimura Masaki
Arerugi = [Allergy]
The case subject was a 19-year-old exchange student from Thailand who had undergone tuberculosis (TB) treatment twice. Upon observing a shadow in the right upper lung, the patient was referred for examination; however, acid-fast bacteria test results were negative. Furthermore, high levels of total IgE and anti-aspergillus IgE and IgG antibodies were found. Bronchoscopy revealed inflammation with stenosis in the right superior lobar bronchus, and there was an outflow of yellow viscous sputum upon suctioning. After applying a localized steroid spray, the patient expectorated a large amount of sputum containing Aspergillus fumigatus. Upon administration of steroids and itraconazole, the conglomerate mass shadow's inner portion disappeared, and dilated bronchi appeared. Even though the diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) of Rosenberg and Patterson were not strictly satisfied, ABPA was diagnosed in conjunction with the course of treatment. It was determined that prior tubercle bacilli test results were negative, and thus the patient must have had ABPA from the onset. The symptoms eased, and the patient returned to Thailand. Although pulmonary tuberculosis and ABPA are different illnesses, they share similarities in symptoms and clinical findings. Therefore, past medical history should not be believed blindly, and it is imperative to diagnosis the condition accurately by performing appropriate tests. Furthermore, we had the opportunity to view the computed tomography images of the chest 18 years after the initial examination. In the entire lung region, findings of significant bronchiectasis were presented.
10.15036/arerugi.70.302
Epidemiology of the relationship between allergic bronchopulmonary aspergillosis and asthma.
Current opinion in allergy and clinical immunology
PURPOSE OF REVIEW:Allergic bronchopulmonary aspergillosis (ABPA) can complicate the natural history of asthmatic patients, especially the more severe ones, worsening disease control and increasing the need for therapies, steroids in particular, and medical care. The aim of the present review is to summarize the latest epidemiological data related to the relationship between asthma and ABPA and to offer a summary of the most recent strategies that could potentially facilitate in the identification of ABPA in asthmatic patients. RECENT FINDINGS:In the last years, great efforts have been made by researchers worldwide to provide reliable epidemiological data on fungal sensitization and ABPA, especially in severe asthma patients both in adult and pediatric population. Data differ depending on the geographical area and population studied, but pooled data show a concerning 11% of severe asthma patients having ABPA and one out of four asthmatic patients being sensitized to fungi, Aspergillus fumigatus in particular. SUMMARY:Reliable epidemiological data and advances in the diagnostic procedures can facilitate the detection of ABPA among asthmatic patients, improving the management of a still under-recognized and challenging condition.
10.1097/ACI.0000000000000971
Allergic bronchopulmonary aspergillosis with atopic, nonatopic, and sans asthma-Factor analysis.
Allergy
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.
10.1111/all.15820
Allergic bronchopulmonary aspergillosis.
Moss Richard B
Clinical reviews in allergy & immunology
Allergic bronchopulmonary aspergillosis (ABPA) is a common complication of cystic fibrosis (CF), occurring in approximately 10% of patients and accompanying/accounting for approximately 10% of pulmonary exacerbations. ABPA pathogenesis is dependent upon impaired clearance and dense respiratory epithelial exposure to A fumigatus (Af) spores with subsequent chemotactic recruitment of CD4+ Th2 lymphocytes specific for Af to lung tissue. Susceptibility to ABPA appears to involve risk factors including atopy and defined major histocompatibility complex-restricted alleles. Distinct cytoplasmic Af molecules (Af2, 4, and 6), now available as recombinant allergen reagents, appear to be associated with ABPA. Minimal criteria for diagnosis of ABPA in CF include clinical deterioration, elevated total serum IgE, positive immediate Af skin test or serum IgE antibodies, and Af serum precipitins/IgG antibodies or radiographic changes. Annual screening of total serum IgE is recommended from age 6 yr. Systemic glucocorticosteroids remain the mainstay of treatment. Itraconazole has an established role as a steroid-sparing agent if the patient has a slow or poor response to steroids, relapses, or is at risk for or develops steroid toxicity. Monitoring of clinical, radiographic and laboratory responses (especially total serum IgE) is essential.
10.1385/CRIAI:23:1:087
Allergic bronchopulmonary aspergillosis.
Agarwal Ritesh
Chest
Allergic bronchopulmonary aspergillosis (ABPA) is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. Clinically, a patient presents with chronic asthma, recurrent pulmonary infiltrates, and bronchiectasis. The population prevalence of ABPA is not clearly known, but the prevalence in asthma clinics is reported to be around 13%. The disorder needs to be detected before bronchiectasis has developed because the occurrence of bronchiectasis is associated with poorer outcomes. Because many patients with ABPA may be minimally symptomatic or asymptomatic, a high index of suspicion for ABPA should be maintained while managing any patient with bronchial asthma whatever the severity or the level of control. This underscores the need for routine screening of all patients with asthma with an Aspergillus skin test. Finally, there is a need to update and revise the criteria for the diagnosis of ABPA. This review summarizes the advances in the diagnosis and management of ABPA using a systematic search methodology.
10.1378/chest.08-2586
Allergic bronchopulmonary aspergillosis.
Greenberger Paul A
The Journal of allergy and clinical immunology
Allergic bronchopulmonary aspergillosis (ABPA) complicates asthma and cystic fibrosis. The survival factors in Aspergillus fumigatus that support saprophytic growth in bronchial mucus are not understood. Prednisone remains the most definitive treatment but need not be administered indefinitely. MHC II -restricted CD4(+) T( H)2 clones have been derived from patients with ABPA. The total serum IgE concentration is elevated sharply but is "nonspecific. " IgE serum isotypic antibodies to A fumigatus are useful in diagnosis; this is in contrast to the situation for patients with asthma without ABPA. High-resolution computed tomography of the chest demonstrates multiple areas of bronchiectasis in most patients with ABPA and is a useful radiologic tool. Some asthma control patients might have a few bronchiectatic airways, but not to the extent seen in or of the same character as those in ABPA. This review discusses clinical, radiologic, investigational, pathogenetic, and treatment issues of ABPA.
10.1067/mai.2002.130179
Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis.
The European respiratory journal
INTRODUCTION:Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear. METHODS:We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21CD4T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures were measured. RESULTS:ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5IL-13IL-21CD4T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5IL-13IL-21CD4T-cells were mainly peripheral T-helper (Tph) cells (PD-1CXCR5), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5IL-13IL-21 Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured , Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION:We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.
10.1183/13993003.00386-2024
Clinical Manifestation and Treatment of Allergic Bronchopulmonary Aspergillosis.
Seminars in respiratory and critical care medicine
Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to airway colonization by in patients with asthma and cystic fibrosis. The pathophysiology of ABPA involves a complex interplay between the fungus and the host immune response, which causes persistent inflammation and tissue damage. Patients present with chronic cough, wheezing, and dyspnea due to uncontrolled asthma. Characteristic symptoms include the expectoration of brownish mucus plugs. Radiographic findings often reveal fleeting pulmonary infiltrates, bronchiectasis, and mucus impaction. However, the definitive diagnosis of ABPA requires a combination of clinical, radiological, and immunological findings. The management of ABPA aims to reduce symptoms, prevent disease progression, and minimize the future risk of exacerbations. The treatment approach involves systemic glucocorticoids or antifungal agents to suppress the inflammatory response or fungal growth and prevent exacerbations. Biological agents may be used in patients with severe disease or glucocorticoid dependence. This review provides an overview of the clinical manifestations and current treatment options for ABPA.
10.1055/s-0043-1776912
Allergic bronchopulmonary aspergillosis in India.
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Allergic bronchopulmonary aspergillosis (ABPA) is a lung disorder caused by immune-mediated reactions mounted against Aspergillus fumigatus. The disorder most commonly complicates the course of patients with asthma and cystic fibrosis. From its first description in 1952, significant advances have been made in understanding the pathogenesis and the diagnosis and treatment of ABPA. In the last two decades, most research on ABPA has been published from India. The prevalence and clinical presentation may differ in India from that reported elsewhere. Herein, we review the epidemiology, clinical and radiological characteristics, and distinctive features of ABPA in the Indian subcontinent. To support the review, we surveyed pulmonologists nationwide to understand the challenges in diagnosing and managing ABPA. The survey has yielded valuable insights into the practices associated with the diagnosis and management of ABPA in India.
10.1111/cea.14319
[Allergic bronchopullmonary aspergillosis (ABPA) - an Update].
Pneumologie (Stuttgart, Germany)
Allergic bronchopulmonary aspergillosis (ABPA) is a regular occurrence in everyday pneumology. ABPA should be considered in patients with severe asthma, in mould allergic patients with very high serum IgE levels and in patients with cystic fibrosis. The aim should be to make the diagnosis as early as possible in the course of the disease to avoid late complications such as bronchiectasis and fibrotic lung remodelling. Symptoms are highly variable and rather non-specific, overlapping with those of the underlying primary disease. However, clearly defined diagnostic criteria exist, so that the diagnosis can be made relatively easily if one thinks of it. In therapy, systemic steroids and antifungals (mainly azoles) play the leading role. However, biologics have been gaining in importance in recent years, especially in cases of insufficient therapy response or occurrence of side effects to standard therapies, as well as an alternative in permanently steroid-dependent patients.
10.1055/a-1854-3006
Allergic bronchopulmonary aspergillosis.
Patel Gayatri,Greenberger Paul A
Allergy and asthma proceedings
Allergic bronchopulmonary aspergillosis (ABPA) occurs in patients with asthma or cystic fibrosis, and results in pulmonary infiltrates, tenacious mucus plugs that harbor hyphae of Aspergillus fumigatus, elevations of total serum immunoglobulin E concentration and peripheral blood and sputum eosinophilia. Bronchiectasis is an irreversible complication of ABPA. The key to early diagnosis is to consider ABPA in anyone with asthma or cystic fibrosis and with a positive skin test result for , and/or recurrent infiltrates on radiographs. The differential diagnosis for ABPA in patients with asthma includes diseases in which there is an overlap of asthma, peripheral blood eosinophilia, and radiographic infiltrates. Examples include chronic eosinophilic pneumonia, Churg-Strauss syndrome, drug-induced pulmonary infiltrates, infection with a parasite, asthma with atelectasis, and lymphoma. Mucus plugging that causes a "tree in bud" pattern on computerized tomography examination of the lungs may be from ABPA or other conditions, such as nontuberculous (atypical) mycobacteria (Mycobacteria avium-Mycobacteria intracellulare complex). Prednisone is indicated to clear pulmonary infiltrates, and a usual course is for 3 months. Itraconazole and voriconazole are adjunctive, and drug-drug interactions must be considered because azoles decrease elimination of various medications. Although not familial in most patients, presentation of Aspergillus fumigatus f1 (Asp f1) antigen is restricted to specific major histocompatibility complex (MHC) class II molecules, Human Leukocyte Antigen-DR2 (HLA-DR2), and HLA-DR5. There is an increased number of CD4 T-helper type 2 lymphocytes in bronchoalveolar lavage, and A. fumigatus can serve as a growth factor of eosinophils potentiating the effects of interleukin (IL) 3, IL-5, and Granulocyte-colony stimulating factor (G-CSF). Eosinophils interact directly with A. fumigatus spores and generate extracellular traps, which can injure the bronchial epithelium.
10.2500/aap.2019.40.4262