What is the recommended treatment for a patient diagnosed with Allergic Bronchopulmonary Aspergillosis (ABPA), particularly those with a history of asthma or cystic fibrosis?

ABPA Diagnosis and Treatment

Diagnosis of ABPA

The diagnosis of ABPA requires meeting specific immunological and radiological criteria, with elevated serum total IgE and Aspergillus-specific antibodies being the cornerstone markers. 1

Essential Diagnostic Criteria

• Immediate cutaneous reactivity to Aspergillus fumigatus on skin testing or elevated serum IgE specific to A. fumigatus 2
• Elevated total serum IgE (typically >1000 IU/mL in untreated cases) 2
• Precipitating serum antibodies to A. fumigatus or elevated serum IgG to A. fumigatus 2
• Peripheral blood eosinophilia as a supportive finding 2

Radiological Classification

ABPA must be classified radiologically to guide treatment decisions 1:

• ABPA-S (Serological ABPA): No bronchiectasis on CT imaging 1
• ABPA-B: Radiological evidence of bronchiectasis 1
• ABPA-MP: Mucus plugging without high-attenuation mucus 1
• ABPA-HAM: High-attenuation mucus plugs (visible on mediastinal windows) 1
• ABPA-CPF: Chronic pleuropulmonary fibrosis with ≥2 of: pulmonary fibrosis, fibro-cavitary lesions, fungal ball, or pleural thickening 1

Common pitfall: In ABPA-CPF, you must exclude chronic pulmonary aspergillosis complicating ABPA, as this changes management entirely 1

---

Treatment of Acute ABPA

For newly diagnosed 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, 3

First-Line Treatment Options

Oral Prednisolone Regimen 1:

• Dose: 0.5 mg/kg/day for 2-4 weeks
• Taper: Gradually reduce over 4 months total duration
• Before initiating: Correct vitamin D deficiency to minimize osteopenia risk 3
• Critical caveat: Avoid methylprednisolone when combined with itraconazole due to increased risk of Cushing's syndrome and adrenal insufficiency 1

Oral Itraconazole Regimen 1:

• Dose: 400 mg/day in two divided doses for 4 months
• Mandatory therapeutic drug monitoring: Target trough level ≥0.5 mg/L 3
• Monthly liver function tests required 3
• Preferred when: Systemic glucocorticoids are contraindicated 1

Combination Therapy

Do NOT use combination therapy (prednisolone + itraconazole) as first-line treatment 1

Exception: A short course of glucocorticoids (<2 weeks) may be added initially with itraconazole for rapid symptom control 1

---

Treatment Based on Disease Classification

Asymptomatic ABPA

Do not treat asymptomatic ABPA patients with systemic therapy; monitoring only is required 1, 3, 4

ABPA-S (Serological ABPA)

Manage ABPA-S like asthma with standard asthma medications (inhaled corticosteroids, bronchodilators) without ABPA-specific systemic therapy 1, 3, 4

Reserve systemic ABPA therapy only when 1:

• Poor asthma control despite optimal asthma management, OR
• Recurrent exacerbations despite optimal asthma therapy

Critical evidence: High-dose inhaled corticosteroids alone have no role in managing ABPA-S and should not be used as first-line therapy, as they do not achieve immunological control or reduce exacerbations 1, 5

---

Monitoring Treatment Response

Assess response at 8-12 weeks using three parameters: clinical symptoms, serum total IgE, and chest radiographs 1, 3, 4

Criteria for Good Response 3:

• Clinical: ≥50% improvement on symptom assessment scale
• Immunological: Serum total IgE decrease ≥20-35% from baseline
• Radiological: Improvement in infiltrates on chest radiographs

---

Management of ABPA Exacerbations

ABPA exacerbations occur in approximately 50% of patients after treatment cessation and should be treated identically to newly diagnosed acute ABPA 1, 4

Defining an Exacerbation

An ABPA exacerbation requires 1, 4:

• Sustained worsening of symptoms ≥2 weeks OR new infiltrates on chest imaging, PLUS
• Serum total IgE increase ≥50% above the "new baseline" IgE (during clinical stability)

Differentiating Types of Exacerbations 1, 4

Asthma exacerbation:

• No increase in serum total IgE
• No new infiltrates on chest imaging
• Manage with short course of oral glucocorticoids

Bronchiectasis (infective) exacerbation:

• Clinical worsening without IgE elevation ≥50%
• Sputum cultures frequently show bacterial growth
• Treat with antibiotics

ABPA exacerbation:

• IgE elevation ≥50% above baseline
• New infiltrates or sustained symptoms ≥2 weeks

Treatment of ABPA Exacerbations

Use prednisolone or itraconazole as for newly diagnosed ABPA 1

For recurrent exacerbations (≥2 in the last 1-2 years), use combination therapy with oral prednisolone AND itraconazole, especially in patients with extensive bronchiectasis 1, 3, 4

Do NOT use 1:

• Biological agents for acute exacerbations
• Nebulized amphotericin B (poor efficacy)

---

Treatment-Dependent ABPA (Maintenance Therapy)

For patients requiring ongoing therapy after initial 4-month treatment 3, 4:

Long-term itraconazole is the preferred maintenance option:

• Reduces oral glucocorticoid dose, sputum eosinophil count, and ABPA exacerbations 4, 6
• Therapeutic drug monitoring is mandatory 4
• Critical for preventing relapses: Lower itraconazole trough levels during first 3 months are associated with increased ABPA recurrence 7

Nebulized liposomal amphotericin B:

• 25 mg weekly significantly prolongs time-to-first exacerbation 4

Biological agents 4:

• Omalizumab has the most evidence: reduces exacerbations, hospitalizations, improves lung function, decreases oral steroid requirements
• Mepolizumab, benralizumab, dupilumab, and tezepelumab have been used successfully
• Not recommended as first-line therapy for acute ABPA 1

---

Advanced ABPA with Extensive Bronchiectasis

Adjunctive Therapies 3, 4

Nebulized hypertonic saline (3-7%, 4-5 mL):

• Reduces sputum viscosity and eases mucus plug expectoration
• Precede with nebulized salbutamol to minimize bronchospasm risk
• Administer first dose under supervision

For frequent infective exacerbations 4:

• Consider nebulized antibiotics
• Consider long-term azithromycin
• Critical caveat: Azithromycin with itraconazole can cause QTc prolongation—monitor ECG

Long-term oxygen therapy (LTOT) 3, 4:

• Recommended for resting hypoxemia (PaO₂ ≤55 mmHg)
• Reduces pulmonary hypertension
• No role in mild hypoxemia (PaO₂ >55 mmHg at rest)

---

Remission Management

During stable disease, monitor with clinical review, serum total IgE, and lung function tests every 3-6 months for the first year, then every 6-12 months 4

Focus on managing underlying asthma and bronchiectasis per existing guidelines 4

Periodic assessments determine ongoing need for antifungal azoles or biological agents 4