What is the evaluation and treatment approach for Allergic Bronchopulmonary Aspergillosis (ABPA)?

Evaluation and Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)

Diagnostic Evaluation

The diagnosis of ABPA requires a combination of clinical presentation (uncontrolled asthma with brownish mucus plugs), elevated serum total IgE (>1000 IU/mL or >500 IU/mL with other criteria), elevated Aspergillus fumigatus-specific IgE, and characteristic CT findings. 1

Essential Diagnostic Criteria

• Serum total IgE >1000 IU/mL is the cornerstone immunological marker; if 500-1000 IU/mL, additional supportive criteria are required 1
• Aspergillus fumigatus-specific IgE elevation using FEIA platform or equivalent automated assays 1
• High-resolution CT chest is mandatory and superior to chest radiography for diagnosis 1, 2

Key Clinical Features to Identify

• Poorly controlled asthma despite standard therapy with recurrent exacerbations 3, 4
• Expectoration of brownish/black mucus plugs is characteristic and highly suggestive 4
• Chronic cough, wheezing, and dyspnea that fails to respond to typical asthma management 4

Radiological Classification (Critical for Prognosis)

The 2024 ISHAM guidelines classify ABPA into five distinct radiological categories 1:

• ABPA-S (Serological): No bronchiectasis on CT 1, 2
• ABPA-B (Bronchiectasis): Radiological evidence of bronchiectasis 1
• ABPA-MP (Mucus Plugging): Mucus plugging without high-attenuation mucus 1
• ABPA-HAM (High-Attenuation Mucus): High-attenuation mucus plugs (>70 HU on mediastinal windows) - pathognomonic for ABPA and predicts severe disease 1, 2
• ABPA-CPF (Chronic Pleuropulmonary Fibrosis): Two or more of: pulmonary fibrosis, fibro-cavitary lesions, fungal ball, pleural thickening 1

High-attenuation mucus is pathognomonic for ABPA and indicates severe disease with higher relapse risk. 2

Additional Imaging Findings

• Central bronchiectasis (traditionally emphasized but peripheral bronchiectasis occurs in 40% of lobes) 2
• Fleeting pulmonary infiltrates, consolidations, centrilobular nodules, tree-in-bud pattern, atelectasis, mosaic attenuation 1

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Treatment Approach

Acute ABPA (Newly Diagnosed or Exacerbation)

Initiate oral prednisolone 0.5 mg/kg/day for 2-4 weeks, then taper over 4 months total duration for acute ABPA. 1, 5

First-Line Glucocorticoid Regimen

• Prednisolone 0.5 mg/kg/day for 2-4 weeks, then taper by 5 mg every 2 weeks until discontinuation at 4 months 1, 6
• This low-to-moderate dose regimen has similar exacerbation rates as higher doses but significantly fewer adverse events 1
• Monitor plasma glucose, blood pressure, body weight, and mental status during glucocorticoid therapy 1

Critical Drug Interaction Warnings

Never combine methylprednisolone with itraconazole due to severe risk of exogenous Cushing's syndrome and adrenal insufficiency. 1, 5

• Avoid combining high-dose inhaled corticosteroids (budesonide/fluticasone) with itraconazole for the same reason 1, 5

Alternative/Adjunctive Therapy: Oral Azoles

• Itraconazole for 4 months is an alternative or can be combined with prednisolone for severe cases 1
• Therapeutic drug monitoring is mandatory: target itraconazole trough >0.5 μg/mL, voriconazole >1 μg/mL, posaconazole >1 μg/mL 1
• Monitor liver function tests in all patients receiving oral azoles 1
• Drug-drug interactions are common; rifampin renders itraconazole undetectable 1

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Response Assessment (8-12 Weeks)

Assess treatment response at 8-12 weeks using clinical symptoms (≥50% improvement), chest radiograph improvement, and ≥35% reduction in serum total IgE from baseline. 1, 5

What to Monitor

• Clinical symptom improvement ≥50% using Likert scale or visual analog scale 1
• Serum total IgE reduction ≥35% from baseline (NOT absolute value) 1, 5
• Chest radiograph showing resolution of infiltrates 1

What NOT to Use for Response Assessment

• Do NOT use Aspergillus fumigatus-specific IgE or IgG for response assessment 1
• Do NOT use peripheral blood eosinophil count for response assessment 1
• Do NOT use IgE against recombinant antigens for response assessment 1

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Treatment-Dependent ABPA (10-25% of Patients)

For treatment-dependent ABPA, use long-term itraconazole, nebulized amphotericin B, or biological agents, with dupilumab (anti-IL-4Rα) emerging as the preferred biologic based on current evidence. 1, 7

Definition

• Patients requiring ongoing therapy to maintain disease control despite initial treatment 1
• ≥2 exacerbations in 1-2 years despite optimal conventional therapy 7, 5

Treatment Options (in Order of Preference)

1. Long-term itraconazole (100% level of consensus): Reduces oral glucocorticoid dose, sputum eosinophils, and exacerbations 1

2. Biological agents (71% level of consensus): 1, 7

   • Dupilumab (anti-IL-4Rα) is the preferred biologic based on emerging evidence suggesting superiority 7
   • Omalizumab (anti-IgE) is the most extensively studied with proven safety even at very high IgE levels; use if dupilumab unavailable 1, 7
   • Other options: Mepolizumab (anti-IL-5), benralizumab (anti-IL-5R), tezepelumab (anti-TSLP) 1
   • Real-world data shows 65% response rate at 12 months with significant reduction in exacerbations and OCS use 8
   • Mucus plugging predicts nonresponse to biologics 8

3. Nebulized amphotericin B (100% level of consensus): 1

   • Amphotericin B deoxycholate 10 mg twice daily, three times weekly OR
   • Liposomal amphotericin B 25 mg weekly
   • Prolongs time-to-first exacerbation 1

4. Continuous low-dose glucocorticoids should be the absolute last resort 1

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Management During Remission

During remission, manage underlying asthma and bronchiectasis per standard guidelines, monitor every 3-6 months in year one, then every 6-12 months thereafter. 1

Monitoring Schedule

• Clinical review, serum total IgE, and lung function tests every 3-6 months for the first year 1, 5
• Then every 6-12 months after the first year 1, 5

Maintenance Therapy

• Continue ICS and long-acting bronchodilators, nebulized saline, antibiotics as needed for underlying asthma/bronchiectasis 1
• Consider long-term itraconazole, nebulized amphotericin B, or biologics to prolong remission, especially in previously treatment-dependent patients 1

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Common Pitfalls and Caveats

Diagnostic Pitfalls

• One-third of patients have normal HRCT (ABPA-S); diagnosis still possible with immunological criteria 2
• Central bronchiectasis is not required; peripheral bronchiectasis occurs frequently 2
• Do not rely on chest radiography alone; HRCT is mandatory 1, 2

Treatment Pitfalls

• Asymptomatic ABPA does not routinely require systemic therapy; treatment decisions must be individualized based on IgE trends and imaging 1
• Shorter glucocorticoid courses (2 weeks) may be sufficient when combined with oral azoles, though 4-month duration is standard 1
• Exclude chronic pulmonary aspergillosis in patients with ABPA-CPF before treating as ABPA alone 1
• Therapeutic drug monitoring is non-negotiable with oral azoles due to variable absorption and drug interactions 1