Allergic Bronchopulmonary Aspergillosis

A hypersensitivity reaction to Aspergillus fumigatus growing in the airway mucus, causing recurrent eosinophilic lung inflammation, mucus plugging, central bronchiectasis and fibrosis.

• Affects about 1 to 2% of adults with asthma (up to 13% in referral asthma clinics) and about 5 to 10% of patients with cystic fibrosis.
• Mechanism: inhaled spores germinate in thick mucus and release antigens, triggering a type 1 (IgE) and type 3 (IgG) response with eosinophil and T helper 2 inflammation.
• Stages: acute, remission, exacerbation, steroid dependent asthma, and fibrotic (end-stage) disease.

Poorly controlled asthma or cystic fibrosis with wheeze, cough, low grade fever, malaise, haemoptysis, and expectoration of brown mucus plugs.

• Examination: wheeze, crackles, bronchial breathing over collapse; clubbing and cor pulmonale in fibrotic stages.
• Differential diagnosis: eosinophilic asthma, tuberculosis, chronic pulmonary aspergillosis, eosinophilic pneumonia, bronchiectasis from other causes, eosinophilic granulomatosis with polyangiitis, fungal sensitisation without disease.
• Complications: recurrent pulmonary infiltrates, central bronchiectasis, lobar collapse, pulmonary fibrosis, respiratory failure, cor pulmonale, aspergilloma, chronic pulmonary aspergillosis, and steroid dependence.

Required: asthma or cystic fibrosis (or compatible disease), total IgE of more than 1000 IU/mL (some use 500 IU/mL), and a positive Aspergillus fumigatus skin test or specific IgE (more than 0.35 kUA/L).

• Plus at least two of: Aspergillus fumigatus IgG (precipitins), blood eosinophils of more than 0.5 x 10^9/L (may be normal on steroids), and compatible chest imaging.
• High-resolution CT: central bronchiectasis with normal peripheral bronchi, high-attenuation mucus (more than 70 Hounsfield units), mucus plugging, collapse and fleeting infiltrates, fibrosis in late disease.
• Sputum fungal culture, spirometry, and exclusion of tuberculosis (Xpert MTB/RIF and AFB smear); itraconazole trough level during treatment; baseline liver tests.

Corticosteroid regimen (first line for acute and exacerbation episodes):

• Prednisolone 0.5 mg/kg daily (usual 30 to 40 mg) for 2 weeks, then 0.5 mg/kg on alternate days for 6 to 8 weeks, then taper by 5 to 10 mg every 2 weeks and stop (total 3 to 5 months); a lower dose regimen of 0.25 mg/kg is an alternative.
• Response is judged by symptoms, chest X-ray clearing in 6 to 8 weeks, and a fall in total IgE of 35% or more at 8 weeks.

```{=html} <!-- --> ``` - Antifungal therapy:

• Itraconazole capsules 200 mg twice daily with food (or solution 200 mg daily on an empty stomach) for 16 weeks as the steroid sparing agent in relapse and steroid dependence; keep the trough above 0.5 mg/L (the target range is 0.5 to 4 mg/L); watch liver function monthly, heart failure and drug interactions (avoid with inhaled budesonide or fluticasone at high dose as it raises steroid levels and causes adrenal suppression).
  • Voriconazole 6 mg/kg twice daily for 2 doses then 4 mg/kg (usual 200 mg) twice daily when itraconazole fails or is not tolerated; target trough 1 to 5.5 mg/L; photosensitivity and visual effects.
• Biologics for steroid dependent or relapsing disease: omalizumab 150 to 600 mg SC every 2 to 4 weeks (by weight and IgE), mepolizumab 100 mg (or 300 mg) SC every 4 weeks, dupilumab 400 mg then 200 mg every 2 weeks (evidence limited).
• Asthma control: inhaled corticosteroid with long-acting beta agonist (budesonide-formoterol 200/6 micrograms 2 puffs twice daily), tiotropium 5 micrograms once daily, montelukast 10 mg at night.
• Airway clearance: hypertonic saline 3% to 7% 4 mL twice daily after salbutamol, chest physiotherapy, bronchoscopic removal of plugs for collapse.
• Steroid safety: calcium 1000 mg and vitamin D 800 units daily; alendronate 70 mg weekly if prolonged; co-trimoxazole 960 mg three times weekly or 480 mg daily for Pneumocystis prophylaxis when prednisolone is 20 mg or more for 4 weeks; blood glucose and pressure checks.
• Cystic fibrosis: prednisolone 0.5 mg/kg daily for 2 weeks then tapered, and itraconazole 200 mg twice daily with trough monitoring, under specialist care, with azole levels and liver function checked monthly.
• Special groups: children (prednisolone 0.5 to 1 mg/kg, itraconazole 5 mg/kg twice daily); pregnancy (prednisolone acceptable; avoid itraconazole and voriconazole, which are teratogenic); elderly (lower steroid doses with bone protection); renal impairment (avoid intravenous itraconazole and voriconazole vehicles); hepatic impairment (monitor azole levels).
• Red flags: haemoptysis, lobar collapse, respiratory failure, rising IgE, new cavity, aspergilloma, treatment relapse.
• Follow-up: total IgE every 6 to 8 weeks for the first year then every 3 months, chest X-ray at 6 to 8 weeks, spirometry each visit, azole levels at 2 weeks and then at changes; relapse in about 30 to 50%, so follow for years.