Allergic Bronchopulmonary Aspergillosis — Branching Viva

Start node — identify the syndrome

Examiner: "What is your working diagnosis, and what must you not assume from the CT alone?"[1]

Expected answer: ABPA is likely, but bronchiectasis and mucus plugs are supportive rather than independently diagnostic. Apply the revised 2024 essentials and supporting components. Do not assume asthma or cystic fibrosis is obligatory, and do not call a fungal ball simple aspergilloma until CPA and ABPA-CPF are considered.[1][8]

Branch rule 1: reveal the A. fumigatus-specific IgE result. If it is at least 0.35 kUA/L, follow Branch A (ABPA). If it is below 0.35 kUA/L despite a convincing allergic mycosis phenotype, follow Branch B (possible ABPM).[1]

Branch A — A. fumigatus-specific IgE is 4.2 kUA/L

Examiner: "Reproduce the revised ABPA criteria."[1]

Expected answer: the entry is asthma, CF, COPD or bronchiectasis, or a compatible clinico-radiological presentation. Both essentials are A. fumigatus-specific IgE at least 0.35 kUA/L and total IgE at least 500 IU/mL. Add any two of A. fumigatus-IgG positivity, current or historical eosinophils at least 500/microL, or compatible thin-section CT/fleeting chest-radiograph opacities. HAM is pathognomonic and can confirm ABPA even if other components are missing.[1]

Examiner: "Could a negative skin-prick test exclude it?"[1]

Expected answer: no. Serum A. fumigatus-specific IgE is preferred because it is more sensitive. A type-1 skin test is an alternative only when specific IgE is unavailable.[1]

Branch A1 — CT mucus is not hyperattenuating

Examiner: "Bronchiectasis and ordinary mucus plugs coexist. Classify it."[1]

Expected answer: ABPA-MP, because non-HAM mucus plugging takes precedence over the bronchiectasis label. ABPA-B is bronchiectasis without mucus plugging; ABPA-S has no bronchiectasis.[1]

Branch A2 — CT mucus is denser than paraspinal muscle

Examiner: "What changes?"[1]

Expected answer: this is ABPA-HAM. HAM is defined visually on non-contrast CT mediastinal windows and is pathognomonic. It is prognostically important, but it does not by itself mandate routine steroid–azole combination therapy.[1]

Branch A3 — CT shows a fungal ball, pleural thickening and fibrosis

Examiner: "Name the class and the exclusion."[1]

Expected answer: at least two chronic pleuropulmonary features suggest ABPA-CPF. Exclude CPA with the clinical time course, Aspergillus evidence and serial imaging; a fungal ball can occur in CPA and is not automatically a simple aspergilloma.[1][8]

Branch B — A. fumigatus-specific IgE is below 0.35 kUA/L

Examiner: "Sputum twice grows Schizophyllum commune. What is the pathway?"[1]

Expected answer: consider ABPM, allergic bronchopulmonary mycosis due a non-Aspergillus fungus. Require elevated IgE to the implicated fungus and total IgE at least 500 IU/mL, then any two of fungus-IgG, eosinophils at least 500/microL, two sputum or one BAL culture growing the causative fungus, or compatible imaging. HAM is pathognomonic. Lack of IgE to rAsp f1, f2 and f4 supports ABPM over ABPA.[1]

Examiner: "Would you order bronchoscopy routinely?"[1]

Expected answer: no. Reserve it for uncertain diagnosis, suspected ABPM with no useful sputum, unexplained haemoptysis, or concern for chronic infection before glucocorticoids.[1]

Treatment node — branch by contraindication and recurrence

Branch rule 2: if acute ABPA is symptomatic and glucocorticoids are acceptable, follow Branch C (prednisolone). If glucocorticoids are contraindicated or unacceptable, follow Branch D (itraconazole). If there have been at least two ABPA exacerbations in the last 1–2 years, follow Branch E (recurrent disease).[1]

Branch C — first acute episode, glucocorticoids acceptable

Examiner: "Give a complete regimen."[2]

Expected answer: prednisolone 0.5 mg/kg/day orally for 2–4 weeks, then taper to finish about 4 months. One validated low-dose regimen continues 0.5 mg/kg on alternate days for 8 weeks and then reduces by 5 mg every 2 weeks over 3–5 months. Monitor glucose, BP, weight, infection, psychiatric, ocular, bone and adrenal risks.[1][2]

Branch D — glucocorticoids contraindicated

Examiner: "Prescribe itraconazole and monitoring."[3]

Expected answer: conventional itraconazole 400 mg/day orally in two divided doses with meals for 4 months. Check liver tests and trough at about 2 weeks and 3 months or during deterioration; target at least 0.5 mg/L. Check formulation, acidity and the complete medication list.[1][3]

Examiner: "She uses high-dose inhaled fluticasone. What can go wrong?"[1]

Expected answer: itraconazole inhibits CYP3A4, increasing fluticasone or budesonide exposure and causing iatrogenic Cushing syndrome and adrenal suppression. It is also a negative inotrope with a heart-failure warning; rifampicin can make itraconazole exposure undetectable.[1]

Branch E — recurrent exacerbations

Examiner: "When is combination therapy appropriate?"[4]

Expected answer: use oral prednisolone plus itraconazole for recurrent ABPA exacerbations — at least two in the previous 1–2 years — particularly with extensive bronchiectasis. Routine combination therapy is not first-line for an uncomplicated first acute episode.[1][4]

Response node — the next question depends on week-8 findings

Branch rule 3: at 8 weeks, compare symptoms, chest radiograph and total IgE. Follow Branch F if formal response is met; follow Branch G if it is not met.[1]

Branch F — symptoms improve 60%; IgE falls 25%

Examiner: "Has she responded?"[1]

Expected answer: yes. Formal response requires symptom improvement at least 50% plus either radiological-opacity improvement over 50% or total IgE decline at least 20% at 8 weeks. Routine clinical review is performed at 8–12 weeks.[1]

Examiner: "When is remission reached?"[1]

Expected answer: after at least 6 months of sustained clinico-radiological improvement off glucocorticoids, with no total IgE rise at least 50% from the stable value. A patient may still be in remission while receiving a long-term azole or biologic.[1]

Branch G — symptoms improve 20%; IgE is unchanged

Examiner: "What do you check before escalating?"[1]

Expected answer: verify adherence, diagnosis, asthma control, bacterial infection, itraconazole formulation/food/acidity, interacting drugs and trough level, liver toxicity, resistant Aspergillus and structural complications. A. fumigatus-specific IgE/IgG and eosinophils are not response markers.[1]

Branch rule 4: if the deterioration lasts over 14 days or imaging worsens and total IgE rises at least 50%, follow Branch H (ABPA exacerbation). If symptoms worsen for at least 48 hours without ABPA immunological/radiological deterioration, follow Branch I (asthma). If cough, sputum or purulence worsens for at least 48 hours without ABPA deterioration, follow Branch J (infective bronchiectasis).[1]

Branch H — ABPA exacerbation

Treat like newly diagnosed ABPA with prednisolone or itraconazole. Do not diagnose from the IgE rise alone; exclude competing causes. Use combination therapy only when the recurrent-exacerbation threshold is met.[1]

Branch I — asthma exacerbation

Manage the asthma exacerbation according to asthma severity. The absence of new ABPA imaging and a less than 50% total-IgE rise argues against ABPA exacerbation.[1]

Branch J — infective bronchiectasis exacerbation

Send sputum bacterial culture and manage bronchiectasis infection and airway clearance. Fever, sputum purulence and increased sputum volume without ABPA immunological/radiological change should not trigger an ABPA steroid course automatically.[1]

Treatment-dependent node

Branch rule 5: reveal the relapse timing. If two consecutive exacerbations each occur within 3 months of stopping glucocorticoids, or taper-associated worsening meets the formal two-occasion definition, follow Branch K.[1]

Branch K — treatment-dependent ABPA

Examiner: "What steroid-sparing options are legitimate?"[5]

Expected answer: long-term itraconazole, maintenance nebulised amphotericin B or a biologic; continuous low-dose oral glucocorticoid is last-line. Omalizumab has the broadest biologic experience and meta-analytic evidence for fewer exacerbations and reduced steroid use, but ABPA use is off-label and not acute first-line therapy. Other options include mepolizumab, benralizumab, dupilumab and tezepelumab with lower-level evidence.[1][5]

Examiner: "Does Cochrane prove omalizumab works especially well in CF-ABPA?"[6]

Expected answer: no. The CF review found one prematurely terminated 14-participant trial with incomplete efficacy data and an adverse-event imbalance; efficacy and safety remain unestablished.[6]

Special-population node

Branch rule 6: reveal pregnancy, childhood or CF before choosing the systemic agent.[1]

Branch L — pregnancy

Use systemic glucocorticoids at the same ABPA dose when treatment is required. Avoid oral azoles and biologics for acute or treatment-dependent ABPA in pregnancy; use multidisciplinary care.[1]

Branch M — child with difficult-to-treat asthma

Use adult treatment principles but protect growth and adrenal/bone health and monitor erratic azole exposure. Screen children for Aspergillus sensitisation only when asthma is difficult to treat; paediatric treatment RCTs are absent.[1]

Branch N — cystic fibrosis

Use glucocorticoid or azole initial therapy with particular attention to steroid-induced diabetes and poor azole absorption/TDM. Do not present a biologic as proven early CF therapy.[1][6]

Aspergillus-spectrum emergency node

Branch rule 7: if a stable cavity contains a mobile ball, follow Branch O. If symptoms and cavity progression persist at least 3 months, follow Branch P. If a high-risk immunocompromised host has rapidly progressive nodules/halo-sign disease, follow Branch Q.[7][8]

Branch O — simple aspergilloma

A stable single fungal ball with minimal surrounding disease may be observed when asymptomatic. Significant haemoptysis in a fit patient favours definitive resection. The mobile ball with surrounding air is the Monod sign, distinct from the recovering-invasive-disease air crescent.[7]

Branch P — CPA

Require at least 3 months of symptoms or radiological progression, compatible cavities/pleural thickening or fungal ball, Aspergillus evidence and exclusion of mimics. CPA often needs long-term antifungal therapy; bronchial-artery embolisation controls acute bleeding but does not replace definitive management.[8]

Branch Q — suspected invasive aspergillosis

Start early mould-active therapy while diagnostic work-up proceeds. Adult voriconazole IV dosing is 6 mg/kg every 12 hours for two loading doses, then 4 mg/kg every 12 hours; oral dosing in adults at least 40 kg is 200 mg every 12 hours with specialist TDM. Alternatives include liposomal amphotericin B and isavuconazonium; echinocandin monotherapy is not routine primary therapy. Treat for at least 6–12 weeks, individualised to response and immunosuppression.[7]

Exit synthesis

Examiner: "Give the safe one-sentence answer."[1]

Expected answer: diagnose ABPA with the revised 2024 two-essential-plus-two-supporting framework, recognise HAM as pathognomonic, classify radiology and activity without old numbered stages, treat acute disease with prednisolone or itraconazole, reserve combination therapy for recurrent exacerbations, and branch any deterioration into ABPA, asthma, infection, CPA/aspergilloma or invasive disease before escalating.[1][7][8]