[Allergic bronchopullmonary aspergillosis (ABPA) - an Update]. / Allergische bronchopulmonale Aspergillose (ABPA) ­ ein Update.

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.

Case Report: Allergic Bronchopulmonary Aspergillosis and Tropical Pulmonary Eosinophilia Co-Occurrence Masquerading as Refractory Allergic Bronchopulmonary Aspergillosis.

Pulmonary infiltrates with eosinophilia are a heterogeneous group of disorders that are characterized by pulmonary infiltrates on chest radiograph and elevated levels of eosinophils in the peripheral blood. Among patients with these disorders, reports of either allergic bronchopulmonary aspergillosis (ABPA) or tropical pulmonary eosinophilia (TPE) are common. However, the simultaneous occurrence of ABPA and TPE is not often reported. We present the case of a young man with a history of asthma who was diagnosed with ABPA and TPE. Initially, the patient exhibited a partial response to treatment of ABPA, but persistent symptoms and eosinophilia led to suspicion and subsequent diagnosis of TPE. With implementation of antifilarials and steroids, the patient experienced satisfactory clinical and serological improvements. This case underscores the importance of considering multiple diagnoses in patients with overlapping symptoms and highlights the need for comprehensive management strategies in complex lung diseases.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Efficacy of omalizumab in adult patients with allergic bronchopulmonary aspergillosis: a multicentre study in China.

Despite conventional glucocorticoid and antifungal therapy, acute exacerbation and hospitalization occur frequently in patients with allergic bronchopulmonary aspergillosis (ABPA). Whether omalizumab is an effective and safe treatment for adult patients with ABPA complicating asthma. Patients with ABPA complicating asthma who were treated with omalizumab from October 2019 to May 2023 were collected from five tertiary hospitals and evaluated. The frequencies of acute exacerbation and hospitalization; the number of eosinophils; the total IgE levels; and the average monthly medical dosages after 3, 6, and 12 months of omalizumab treatment were analysed, and the data before and after treatment (up to one year) were compared. The efficacy and safety of omalizumab treatment were assessed. In total, 26 patients were enrolled. The average monthly glucocorticoid dosage significantly decreased (median 0 vs. 24 mg/m) after 6 months of omalizumab treatment compared with 3 months; 73.68% of patients discontinued glucocorticoids after ≤ 12 months of treatment. Similarly, the average monthly dosage of antifungal agents was significantly decreased (median 0 vs. 3.49 g/m) after 12 months of treatment compared with 3 months. The average monthly glucocorticoid dosage (median 213.75 vs. 65.42 mg/m, P = 0.002) and the frequency of acute exacerbation (median 0.94 vs. 0.44 events, P = 0.033) were considerably reduced after omalizumab treatment. Omalizumab is effective in reducing the frequency of acute exacerbation and the necessary dosage of glucocorticoids in adult patients with ABPA complicating asthma. Patient age and BMI may affect the efficacy of treatment.

Antifungal Resistance in Pulmonary Aspergillosis.

Aspergilli may cause various pulmonary diseases in humans, including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and acute invasive pulmonary aspergillosis (IPA). In addition, chronic colonization may occur in cystic fibrosis (CF). Aspergillus fumigatus represents the main pathogen, which may employ different morphotypes, for example, conidia, hyphal growth, and asexual sporulation, in the various Aspergillus diseases. These morphotypes determine the ease by which A. fumigatus can adapt to stress by antifungal drug exposure, usually resulting in one or more resistance mutations. Key factors that enable the emergence of resistance include genetic variation and selection. The ability to create genetic variation depends on the reproduction mode, including, sexual, parasexual, and asexual, and the population size. These reproduction cycles may take place in the host and/or in the environment, usually when specific conditions are present. Environmental resistance is commonly characterized by tandem repeat (TR)-mediated mutations, while in-host resistance selection results in single-resistance mutations. Reported cases from the literature indicate that environmental resistance mutations are almost exclusively present in patients with IA indicating that the risk for in-host resistance selection is very low. In aspergilloma, single-point mutations are the dominant resistance genotype, while in other chronic Aspergillus diseases, for example, ABPA, CPA, and CF, both TR-mediated and single-resistance mutations are reported. Insights into the pathogenesis of resistance selection in various Aspergillus diseases may help to improve diagnostic and therapeutic strategies.

Clinical Manifestation and Treatment of Allergic Bronchopulmonary Aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to airway colonization by Aspergillus fumigatus 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.

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.

Iatrogenic Cushing's syndrome in a case of allergic bronchopulmonary aspergillosis treated with oral itraconazole and inhaled budesonide.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus that occurs in patients with asthma or cystic fibrosis. Here, we report a case of a young female with bronchial asthma who presented to our hospital with worsening breathlessness on exertion. She was diagnosed to have ABPA and was initiated on oral itraconazole while continuing inhaled long acting beta-2 adrenergic agonist and medium dose inhaled corticosteroid (ICS) for her asthma. Three months after initiation of therapy, the patient had significant improvement in breathlessness. However, she had weight gain, facial puffiness, increased facial hair and development of striae on her inner thighs, calf and lower abdomen. Her serum cortisol levels were found to be suppressed and hence a diagnosis of iatrogenic Cushing's syndrome was made. Our case describes the potentially serious interaction between ICS and oral itraconazole, a treatment very commonly prescribed in patients with ABPA.

Simultaneous diagnosis of allergic bronchopulmonary aspergillosis and Mycobacterium avium complex lung disease.

Allergic bronchopulmonary aspergillosis (ABPA) and Mycobacterium avium complex lung disease (MAC-LD) often coexist because bronchiectasis, caused by ABPA or MAC, might be an important predisposing factor for both conditions. Here, we describe a man with asthma symptoms who had centrilobular small nodules and mucoid impaction on chest CT. We diagnosed the patient with simultaneous ABPA and MAC-LD on the basis of bronchoscopy findings. Itraconazole monotherapy led to substantial clinical improvement, avoiding the adverse effects of systemic corticosteroids. Sputum culture conversion of MAC was achieved after switching from itraconazole monotherapy to combination therapy comprising clarithromycin, rifampicin and ethambutol. ABPA recurred but was controlled by reinitiation of itraconazole. Overall, corticosteroid management was avoided for 38 months. Itraconazole monotherapy may be selected as initial treatment for ABPA with chronic infection, including MAC.

Relationship between Aspergillus and asthma.

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.

Evidence-Based Guidelines for the Management of Allergic Bronchopulmonary Aspergillosis (ABPA) in Children and Adolescents with Asthma.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) frequently complicates asthma. There is urgent need to develop evidence-based guidelines for the management of ABPA in children. The Evidence Based Guideline Development Group (EBGDG) of the Indian Academy of Pediatrics (IAP) National Respiratory Chapter (NRC) addressed this need. METHODS: The EBGDG shortlisted clinical questions relevant to the management of ABPA in asthma. For each question, the EBGDG undertook a systematic, step-wise evidence search for existing guidelines, followed by systematic reviews, followed by primary research studies. The evidence was collated, critically appraised, and synthesized. The EBGDG worked through the Evidence to Decision (EtD) framework, to formulate recommendations, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Seven clinical questions were prioritized, and the following recommendations formulated. (1) Children with poorly controlled asthma should be investigated for ABPA (conditional recommendation, moderate certainty of evidence). (2) Low dose steroid therapy regimen (0.5 mg/kg/d for the first 2 wk, followed by a progressive tapering) is preferable to higher dose regimens (conditional recommendation, very low certainty of evidence). (3) Oral steroid regimens longer than 16 wk (including tapering), should not be used (conditional recommendation, very low certainty of evidence). (4) Antifungals may or may not be added to steroid therapy as the evidence was neither in favour nor against (conditional recommendation, low certainty of evidence). (5) For clinicians using antifungal agents, the EBGDG recommends against using voriconazole instead of itraconazole (conditional recommendation, very low certainty of evidence). (6) No evidence-based recommendation could be framed for using pulse steroid therapy in preference to conventional steroid therapy. (7) Immunotherapy with biologicals including omalizumab or dupilumab is not recommended (conditional recommendation, very low certainty of evidence). CONCLUSIONS: This evidence-based guideline can be used by healthcare providers in diverse clinical settings.

Allergic bronchopulmonary aspergillosis: A multidisciplinary review.

Allergic bronchopulmonary aspergillosis (ABPA) is a rare disease characterized by a complex allergic inflammatory reaction of airways against Aspergillus affecting patients with chronic respiratory diseases (asthma, cystic fibrosis). Exacerbation is often the way to diagnose ABPA and marks its evolution by its recurrent character leading to cortico-requirement or long-term antifungal treatment. Early diagnosis allows treatment of ABPA at an initial stage, preventing recurrence of exacerbations and long-term complications, mainly represented by bronchiectasis. This review of the literature aims to present the current state of the art in terms of diagnosis and treatment of ABPA from a multidisciplinary perspective. As there is no clinical, biological nor radiological specific sign, diagnostic criteria are regularly revised. They are mainly based on the elevation of total and specific IgE against Aspergillus fumigatus and the presence of suggestive CT abnormalities such as mucoid impaction and consolidations. ABPA management includes eviction of mold and pharmacological therapy. Exacerbations are treated in first line with a moderate dose of oral corticosteroids. Azole antifungal agents represent an alternative for the treatment of exacerbations and are the preferential strategy to reduce the future risk of exacerbations and for corticosteroids sparing. Asthma biologics may be of interest; however, their place remains to be determined. Avoiding complications of ABPA while limiting the side effects of systemic drugs remains a major challenge of ABPA management. Several drugs, including new antifungals and asthma biologics, are currently being tested and may be useful in the future.

Nebulized amphotericin B for preventing exacerbations in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is complicated by exacerbations in more than one-third of the subjects. Whether nebulized amphotericin B (NAB) therapy prevents ABPA exacerbations remains unclear. OBJECTIVES: The primary objective of this systematic review and meta-analysis was to determine the frequency of subjects remaining exacerbation-free, one year after initiating NAB. The key secondary objectives were the time to first exacerbation and the safety of NAB therapy. METHODS: We searched the PubMed and Embase databases for studies evaluating ≥5 subjects of ABPA managed with NAB. We report the pooled proportion of ABPA subjects remaining exacerbation free after one year. For the randomized controlled trials (RCTs), we estimate the pooled risk difference (RD) of exacerbation-free status at one year with NAB versus the control arm. RESULTS: We included five studies for our analysis; three were observational (n = 28) and two RCTs (n = 160). The pooled proportion (95% confidence interval [CI]) of subjects remaining exacerbation free with NAB at one year was 76% (62-88). The pooled RD (95% CI) of an exacerbation-free status at one year was 0.33 (-0.12 to 0.78) and was not significantly different between the NAB and control arms. The time to first exacerbation was longer with NAB than with the standard therapy. No serious adverse events were reported with NAB. CONCLUSION: NAB does not improve exacerbation-free status at one year; however, weak evidence suggests it delays ABPA exacerbations. More research using different dosing regimens is required.

Real-world efficacy of anti-IL-5 treatment in patients with allergic bronchopulmonary aspergillosis.

Despite standard treatment with systemic corticosteroids and/or antifungal triazoles, a substantial proportion of patients with allergic bronchopulmonary aspergillosis (ABPA) experience frequent relapses and require long-term treatment despite unfavorable adverse effects. We investigated the efficacy and safety of anti-interleukin (IL)-5/IL-5 receptor α chain (Rα) monoclonal antibodies (mAbs) in patients with ABPA complicated by asthma. ABPA cases treated with anti-IL-5/IL-5Rα mAbs were collected from 132 medical institutes in 2018 and published case reports in Japan. Clinical outcomes, laboratory and physiological data, and radiographic findings during 32 weeks before and after treatment were retrospectively evaluated. We analyzed 29 cases of ABPA: 20 treated with mepolizumab and nine with benralizumab. Treatment with anti-IL-5/IL-5Rα mAbs reduced the frequency of exacerbations (p = 0.03), decreased the dose of oral corticosteroids (p < 0.01), and improved pulmonary function (p = 0.01). Mucus plugs in the bronchi shrank or diminished in 18 patients (82%). Despite the clinical/radiographical improvement, serum levels of total IgE, the key biomarker for the pharmacological response in ABPA, were unchanged. Anti-IL-5/IL-5Rα mAbs that directly target eosinophils are promising candidates for the treatment of patients with ABPA, especially those with mucus plugs in the bronchi.