What is the recommended treatment for allergic bronchopulmonary aspergillosis (ABPA)?

Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)

Oral glucocorticoids are the most rapid-acting first-line treatment for acute ABPA, with oral itraconazole recommended as an alternative first-line option with fewer adverse events but slower onset of action. 1

Initial Treatment for Acute ABPA

First-Line Options:

1. Oral Prednisolone (preferred for rapid symptom control):

   • Dosage: 0.5 mg/kg/day for 2-4 weeks
   • Taper: Complete over 4 months
   • Monitoring: Blood glucose, blood pressure, weight, mental status 1

2. Oral Itraconazole (alternative with better safety profile):

   • Conventional capsules: 400 mg/day in two divided doses for 4 months
   • Super bioavailable capsules: 260 mg/day in two divided doses for 4 months (on empty stomach)
   • Monitoring: Liver function tests, therapeutic drug levels (target >0.5 μg/mL) 1

Treatment Response Assessment:

• Evaluate after 8-12 weeks using:
  • Clinical improvement (≥50% symptom reduction)
  • Chest radiograph improvement
  • ≥20% reduction in serum total IgE 1

Management of Treatment-Dependent ABPA (10-25% of patients)

For patients requiring ongoing therapy or experiencing recurrent exacerbations:

1. Long-term itraconazole (200 mg daily)
2. Nebulized amphotericin B:
   • Liposomal formulation: 25 mg weekly
   • Conventional deoxycholate: 10 mg twice daily, three times weekly 1
3. Biological agents for steroid-dependent patients:
   • Omalizumab (most evidence in ABPA)
   • Mepolizumab, benralizumab, dupilumab, or tezepelumab 1, 2

Management of ABPA with Extensive Bronchiectasis

1. Airway clearance techniques
2. Nebulized hypertonic saline (3-7%, 4-5 mL)
   • Precede with nebulized salbutamol to prevent bronchospasm
   • First dose under supervision 1, 2
3. Consider nebulized antibiotics or long-term azithromycin for frequent infective exacerbations
   • Caution: Azithromycin + itraconazole may cause QTc prolongation 1

Monitoring During Remission

• Clinical review, serum total IgE, and lung function tests:
  • Every 3-6 months for the first year
  • Every 6-12 months thereafter 1
• Manage underlying asthma and bronchiectasis according to standard guidelines 1

Important Considerations and Pitfalls

1. Drug Interactions:

   • Itraconazole + inhaled budesonide/fluticasone: Risk of Cushing's syndrome
   • Methylprednisolone + itraconazole: Higher risk of exogenous Cushing's syndrome
   • Azithromycin + itraconazole: QTc prolongation risk 1, 2

2. Therapeutic Drug Monitoring:

   • Minimum therapeutic levels: >0.5 μg/mL for itraconazole, >1 μg/mL for voriconazole/posaconazole
   • Inadequate levels may lead to treatment failure 1, 2

3. Asymptomatic ABPA:

   • Generally does not require systemic therapy
   • Consider treatment if CT shows bronchiectasis or mucus plugging
   • If untreated: Monitor with clinical review, chest radiograph, and serum total IgE every 3-6 months 1

4. High-dose inhaled corticosteroids alone:

   • Not effective as primary therapy for acute ABPA
   • May be used for maintenance after initial control with systemic therapy 1, 3

Special Situations

Corticosteroid-Resistant ABPA

For patients not responding to conventional therapy:

• Consider combination of prednisolone and itraconazole 1
• Consider pulse intravenous methylprednisolone (though side effects may limit use) 4
• Biological agents may be particularly beneficial 1, 2

ABPA in Cystic Fibrosis

• Short-term prednisone (18 days) combined with long-term itraconazole (≥12 months) can be effective
• Therapeutic drug monitoring of itraconazole is crucial to prevent relapses
• Lower itraconazole levels during the first 3 months associated with higher relapse risk 5

By following this structured approach to ABPA management, clinicians can effectively control symptoms, prevent exacerbations, and minimize progression to irreversible bronchiectasis while balancing treatment efficacy against potential adverse effects.