What is the recommended management for Allergic Bronchopulmonary Aspergillosis (ABPA)?

Management of Allergic Bronchopulmonary Aspergillosis (ABPA)

The cornerstone of ABPA management is oral prednisolone (0.5 mg/kg/day for 2-4 weeks, tapered over 4 months) combined with itraconazole (400 mg/day for 4 months) for acute exacerbations, with treatment selection guided by disease classification and severity. 1, 2

Initial Classification and Treatment Strategy

Classification determines treatment approach:

• ABPA-S (without bronchiectasis): Manage as asthma unless poor control or recurrent exacerbations occur 1
• ABPA-B (with bronchiectasis): Requires active ABPA-specific treatment 1
• Asymptomatic ABPA: No systemic therapy indicated 1

Acute ABPA Treatment

First-Line Options

Oral prednisolone is the primary treatment:

• Start at 0.5 mg/kg/day for 2-4 weeks 1, 2
• Taper gradually over remaining period to complete 4-month total course 1, 2
• Monitor serum total IgE every 6-8 weeks as disease activity marker 2

Itraconazole as monotherapy or combination:

• Dose: 400 mg/day in two divided doses for 4 months 1, 2
• Use as first-line when systemic glucocorticoids are contraindicated 1
• Consider combination therapy for patients with blood eosinophils ≥1000 cells/μL and extensive bronchiectasis (≥10 segments) 1
• Requires therapeutic drug monitoring with target trough level ≥0.5 mg/L 2

The evidence strongly supports combination therapy. Multiple studies demonstrate that itraconazole reduces oral glucocorticoid requirements, with 50% of patients able to discontinue steroids entirely while maintaining clinical improvement 3. In CF patients, combination therapy restored FEV1 to pre-ABPA levels within 3 months without typical glucocorticoid side effects 4.

Monitoring Treatment Response

Assess response at 8-12 weeks using: 1

• Clinical symptoms (≥50% improvement on Likert scale indicates good response)
• Serum total IgE levels (≥20% reduction indicates good response)
• Chest radiographs for infiltrate resolution

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

Long-term itraconazole is the preferred maintenance option: 5

• Reduces oral glucocorticoid dose, sputum eosinophil count, and ABPA exacerbations 5
• Therapeutic drug monitoring is mandatory (LoC: 91.4%) 5

Alternative maintenance options:

• Nebulized amphotericin B: Liposomal formulation 25 mg weekly significantly prolongs time-to-first exacerbation 5
• Biological agents (LoC: 71%): 5
  • Omalizumab has the most evidence: reduces exacerbations, hospitalizations, improves lung function, and decreases oral steroid requirements 5
  • Mepolizumab, benralizumab, dupilumab, and tezepelumab have been used successfully 5
  • Consider for maintenance therapy of underlying severe asthma 5

Continuous low-dose glucocorticoids should be the last resort for managing treatment-dependent ABPA 5

ABPA Exacerbations

Definition: Sustained worsening (≥2 weeks) of clinical symptoms or new infiltrates on chest imaging, plus serum total IgE increase ≥50% above the "new baseline" during clinical stability 1

Treatment approach:

• Treat with oral prednisolone or itraconazole 1
• Consider combination therapy for recurrent exacerbations 1
• Differentiate from asthma exacerbations and infective bronchiectasis exacerbations using chest radiographs, serum total IgE, and sputum cultures 1

Approximately 50% of patients experience exacerbations after treatment cessation 1

Remission Management

During stable disease, focus on underlying conditions: 5

• Manage asthma and bronchiectasis per existing guidelines (ICS, long-acting bronchodilators, nebulized saline, antibiotics) 5
• Monitor with clinical review, serum total IgE, and lung function tests every 3-6 months for the first year, then every 6-12 months 5
• Periodic assessments to determine ongoing need for antifungal azoles or biological agents (LoC: 100%) 5

Remission is defined as: No pulmonary infiltrates and/or eosinophilia for 6 months after oral steroid withdrawal 2

Advanced ABPA with Extensive Bronchiectasis

Adjunctive therapies:

• Nebulized hypertonic saline (3-7%, 4-5 mL): Reduces sputum viscosity and eases mucus plug expectoration 5
  • Precede with nebulized salbutamol to minimize bronchospasm risk 5
  • Administer first dose under supervision 5
• Nebulized antibiotics and long-term azithromycin: For patients with frequent infective exacerbations 5
  • Critical caveat: Azithromycin with itraconazole can cause QTc prolongation 5

For advanced disease with respiratory failure:

• Long-term oxygen therapy (LTOT) for resting hypoxemia (PaO2 ≤55 mmHg) reduces pulmonary hypertension 5
• No role for LTOT in mild hypoxemia (PaO2 >55 mmHg at rest) 5
• Administer influenza and pneumococcal vaccines before initiating glucocorticoids or after disease control 5
• Use International Society for Heart and Lung Transplantation criteria for transplant referral 5

Critical Pitfalls to Avoid

Drug interactions and monitoring:

• Never use methylprednisolone with itraconazole due to higher risk of exogenous Cushing's syndrome 2
• Avoid high-dose inhaled corticosteroids with itraconazole due to drug interactions 2
• Monitor liver function tests monthly on itraconazole 2
• Ensure therapeutic drug monitoring for itraconazole—lower trough levels in first 3 months predict ABPA relapses 4

Treatment considerations:

• Monitor for osteopenia with oral corticosteroids and correct vitamin D deficiency 1
• Asymptomatic patients with prolonged mucus plugging may still require treatment to prevent irreversible bronchiectasis 2
• IgE against recombinant antigens are not recommended for response assessment 5