Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA)
For acute ABPA, initiate either oral prednisolone 0.5 mg/kg/day for 2–4 weeks (tapered over 4 months total) or oral itraconazole 400 mg/day for 4 months as first-line monotherapy. 1, 2
Treatment Algorithm Based on ABPA Classification
Asymptomatic ABPA
- Do not treat with systemic therapy—monitor only with clinical review, chest radiograph, and serum total IgE every 3–6 months. 1, 2
Serological ABPA Without Bronchiectasis (ABPA-S)
- Manage as standard asthma with high-dose inhaled corticosteroids and bronchodilators. 1, 3
- Reserve systemic ABPA-directed therapy (prednisolone or itraconazole) only for patients with poor asthma control despite optimal inhaled therapy or recurrent exacerbations. 1, 4
- High-dose inhaled corticosteroids alone do not achieve immunological control or reduce ABPA exacerbations and should never be used as primary ABPA therapy. 1, 5
Acute ABPA With Bronchiectasis or Mucus Plugging
- Systemic treatment is mandatory even if the patient is otherwise asymptomatic, to prevent progression to irreversible bronchiectasis. 2, 4
First-Line Treatment Options for Acute ABPA
Option 1: Oral Prednisolone (Preferred When Rapid Control Needed)
- Dose: 0.5 mg/kg/day (approximately 35 mg daily for a 70 kg adult) for 2–4 weeks, then taper over a total duration of 4 months. 1, 2
- Tapering strategy:
- Bone protection: Prescribe calcium 1000–1500 mg/day and vitamin D 800–1000 IU/day from day 1 of steroid therapy. 2
- Monitoring: Check serum total IgE every 6–8 weeks; a ≥35% reduction from baseline indicates good response, while a ≥50% rise above stable baseline suggests exacerbation. 2, 4
Option 2: Oral Itraconazole (Preferred When Steroids Contraindicated)
- Dose: 400 mg/day in two divided doses (200 mg twice daily with meals) for 4 months. 1, 2
- Therapeutic drug monitoring: Check trough level after 2 weeks; target ≥0.5 mg/L (ideal 1–2 mg/L). 2, 3
- Liver monitoring: Perform monthly liver function tests due to hepatotoxicity risk. 2, 4
- Absorption: Use conventional itraconazole capsules taken with meals to improve absorption. 2
Critical Drug Interaction Warning
Never combine itraconazole with methylprednisolone—this markedly increases the risk of exogenous Cushing's syndrome and adrenal insufficiency. 1, 2
- Itraconazole does not significantly affect prednisolone levels, making prednisolone the preferred corticosteroid when combination therapy is required. 2
- Do not combine itraconazole with high-dose inhaled corticosteroids (budesonide or fluticasone) due to cytochrome P450 inhibition causing adrenal suppression. 2, 4
When to Use Combination Therapy (Prednisolone + Itraconazole)
Combination therapy is NOT recommended as first-line treatment. 1, 2
- A short course (<2 weeks) of oral glucocorticoids may be added when initiating itraconazole to achieve rapid symptom control, then transition to high-dose inhaled corticosteroids once symptoms improve. 1, 2
Indications for Combination Therapy:
- ≥2 ABPA exacerbations in the past 1–2 years. 1, 2
- Extensive bronchiectasis involving ≥10 lung segments. 2, 4
- Blood eosinophil count ≥1000 cells/µL together with extensive bronchiectasis. 2, 4
- Steroid-dependent disease (difficulty weaning from corticosteroids or relapse upon dose reduction). 2
Assessment of Treatment Response
Evaluate response at 8–12 weeks using the following criteria: 1, 4
- Clinical improvement: ≥50% reduction in symptoms on assessment scale. 2, 4
- Serum total IgE: Reduction ≥20% from baseline (≥35% preferred). 2, 4
- Chest imaging: Resolution of infiltrates. 2, 4
- Spirometry: FEV₁ improvement ≥158 mL (minimal clinically important difference). 2
Continue monitoring every 3–6 months with clinical review, serum IgE, lung function tests, and chest imaging as indicated. 2, 3
Management of ABPA Exacerbations
Definition of Exacerbation:
An ABPA exacerbation requires all three of the following: 1, 2
- Persistent worsening of respiratory symptoms for ≥2 weeks.
- New pulmonary infiltrates on imaging.
- Serum total IgE rise ≥50% above the patient's "new baseline" during clinical stability.
Distinguishing Exacerbation Types:
- Asthma exacerbation: No IgE rise, no new infiltrates—treat with short-course oral glucocorticoids. 1
- Bronchiectasis infective exacerbation: No IgE rise, positive sputum cultures—treat with antibiotics. 1
- ABPA exacerbation: IgE rise ≥50%, new infiltrates—treat as newly diagnosed ABPA. 1, 2
Treatment of Exacerbations:
- Treat like newly diagnosed acute ABPA with either prednisolone or itraconazole monotherapy. 1, 2
- For recurrent exacerbations (≥2 in 1–2 years), especially with extensive bronchiectasis, use combination therapy (prednisolone + itraconazole). 1, 2
- Approximately 50% of patients experience exacerbations after treatment cessation, necessitating retreatment. 1, 2
Second-Line Antifungal Options
Voriconazole, posaconazole, and isavuconazole are NOT first-line agents. 1, 4
- Reserve these for patients who cannot receive systemic glucocorticoids or who have intolerance, failure, or resistance to itraconazole. 1, 2
| Antifungal | Recommended Dose | Maximum Dose |
|---|---|---|
| Voriconazole | 400 mg/day (200 mg twice daily) | 600 mg/day |
| Posaconazole | 800 mg/day (oral suspension, two divided doses with meals) or 300 mg/day (delayed-release tablet once daily) | — |
| Isavuconazole | 200 mg once daily (no food restrictions) | — |
Role of Biological Agents
Biological agents are NOT first-line therapy. 1, 2
- Consider for treatment-dependent ABPA (patients requiring ongoing therapy after initial 4-month treatment or who relapse upon dose reduction). 2, 3
- Omalizumab: Dose based on body weight and serum IgE, not exceeding 375 mg subcutaneously twice monthly. 2
- Mepolizumab: 100 mg subcutaneously monthly. 2
- Dupilumab: 600 mg loading dose subcutaneously, then 300 mg every 2 weeks. 2
- Approximately 10–25% of ABPA patients become treatment-dependent. 3, 4
Common Pitfalls to Avoid
- Tapering prednisolone too quickly leads to relapse—reduce by 5 mg increments every 2–6 weeks, not faster. 2
- Ignoring rising IgE trends during taper signals impending exacerbation—slow or reverse the taper immediately. 2
- Using methylprednisolone with itraconazole precipitates severe Cushing's syndrome—always use prednisolone instead. 2, 4
- Neglecting bone protection—always prescribe calcium and vitamin D at steroid initiation. 2
- Using high-dose inhaled corticosteroids alone as primary ABPA therapy—this does not control disease and should never be done. 1, 5
- Failing to distinguish between asthma exacerbations, ABPA exacerbations, and infective bronchiectasis exacerbations—use IgE levels, chest imaging, and sputum cultures to differentiate. 1, 4