How is allergic bronchopulmonary aspergillosis with chronic pulmonary fibrosis (ABPA‑CPF) diagnosed and managed in adults with long‑standing asthma or cystic fibrosis?

ABPA-CPF: Diagnosis and Management

What is ABPA-CPF?

ABPA-CPF (Allergic Bronchopulmonary Aspergillosis with Chronic Pleuropulmonary Fibrosis) represents the most advanced stage of ABPA, characterized by irreversible fibrotic changes, cavitation, and pleural thickening that develops after years of untreated or inadequately controlled disease. 1, 2

This stage marks a critical transition where the primarily allergic/inflammatory disease has caused permanent structural lung damage including fibro-cavitary lesions, fungal balls, and extensive fibrosis. 2

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Diagnostic Approach to ABPA-CPF

Mandatory Immunological Criteria

The diagnosis requires demonstration of the underlying ABPA process:

• Total serum IgE ≥500 IU/mL (mandatory criterion, though may be lower in end-stage fibrosis) 1
• Elevated A. fumigatus-specific IgE (mandatory for ABPA diagnosis) 1, 3
• Elevated A. fumigatus-specific IgG (one of two additional required criteria) 1
• Peripheral blood eosinophilia (supports ABPA over other diagnoses) 3

Critical Differential: Excluding Chronic Pulmonary Aspergillosis (CPA)

When ABPA progresses to a cavitary phenotype (ABPA-CPF), you must actively exclude CPA by comparing immunological profiles—dominant IgE elevation plus eosinophilia favors ABPA-CPF, whereas predominant IgG without marked IgE elevation favors CPA. 2

Key distinguishing features:

• ABPA-CPF: Markedly elevated total IgE (often >1000 IU/mL), elevated Aspergillus-specific IgE, peripheral eosinophilia, history of asthma or CF 2, 3
• CPA: Elevated Aspergillus-specific IgG (>90% positive), absent or minimal IgE elevation, no eosinophilia, no asthma/CF history 2, 3

This distinction is critical because using corticosteroids in CPA patients can worsen infection and potentially lead to invasive aspergillosis, whereas corticosteroids are first-line for ABPA-CPF. 3

Radiological Features of ABPA-CPF

Perform thin-section chest CT (1.25-1.5 mm slice thickness) with contrast to identify the characteristic features of advanced ABPA. 4

ABPA-CPF demonstrates:

• Fibrosis and fibro-cavitary lesions (defining feature of CPF stage) 2, 4
• Fungal balls (aspergillomas) within cavities 2
• Pleural thickening 2, 4
• Central bronchiectasis (bilateral, upper/middle lobe predominant—the hallmark of underlying ABPA) 2, 4
• High-attenuation mucus (denser than paraspinal muscle—pathognomonic when present) 2, 4

The 2024 ISHAM-ABPA Working Group classifies this as ABPA-CPF, the most severe CT-based category. 4

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Management of ABPA-CPF

Treatment Strategy

Oral corticosteroids remain first-line therapy even in the fibrotic stage to control ongoing allergic inflammation, combined with itraconazole to reduce fungal burden. 1, 5

Corticosteroid Regimen

• Oral prednisolone 0.5 mg/kg/day for 2-4 weeks, then taper over approximately 4 months 2, 5
• Long-term maintenance may be required for recurrent exacerbations 5, 6

Antifungal Therapy

• Itraconazole as adjunctive therapy to reduce A. fumigatus colonization and serve as a corticosteroid-sparing agent 1, 2, 5
• Consider long-term azole therapy (itraconazole or voriconazole) given the cavitary nature mimicking CPA 2

Biologic Agents for Refractory Disease

• Anti-IL-5 or anti-IgE monoclonal antibodies (e.g., omalizumab) for patients with inadequate response to corticosteroids or intolerable side effects 2, 6, 7
• Emerging evidence supports biologics for reducing exacerbation frequency in CF patients with ABPA 7

Treatment Monitoring

Use chest radiographs, not CT, for routine treatment monitoring to minimize cumulative radiation exposure. 4

Reserve repeat CT for:

• New hemoptysis 4
• Suspected treatment failure 4
• Significant clinical deterioration 4

Assessing Treatment Response

The 2024 ISHAM-AWG guidelines recommend an objective multidimensional criterion to assess treatment response, evaluating clinical symptoms, IgE levels, eosinophil counts, and radiological changes. 1

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Key Clinical Pitfalls

Do Not Treat Asymptomatic ABPA

The 2024 guidelines do not recommend routinely treating asymptomatic ABPA patients, even if serological criteria are met. 1 However, ABPA-CPF typically represents symptomatic, advanced disease requiring treatment.

Recognize the Predisposing Conditions

ABPA-CPF develops almost exclusively in patients with:

• Long-standing asthma (most common) 1, 5, 6
• Cystic fibrosis (approximately 7-9% prevalence of ABPA) 4, 8, 7
• Occasionally non-CF bronchiectasis or COPD 1

Prevention is Key

If ABPA is diagnosed and treated before the development of bronchiectasis and fibrosis, progression to ABPA-CPF may be prevented. 5 This underscores the importance of screening difficult-to-treat asthmatic children and all newly diagnosed asthmatic adults at tertiary care for A. fumigatus sensitization. 1

Avoid Misdiagnosis as Pulmonary Exacerbation

In CF patients, ABPA exacerbations mimic routine pulmonary exacerbations, leading to delayed diagnosis. 8 Maintain high suspicion when clinical and radiologic deterioration occurs without another clear etiology, especially with markedly elevated total IgE. 7

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Prognosis and Long-Term Considerations

The natural history of ABPA-CPF involves:

• Irreversible structural lung damage with fibrosis and cavitation 2, 5
• Progressive loss of lung function if inadequately controlled 8, 9
• Recurrent exacerbations requiring ongoing immunosuppression 6

The goal is to arrest further inflammation and prevent additional fibrotic progression, though existing structural damage cannot be reversed. 2, 5