What are the differences between allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA)?

Distinguishing ABPA from CPA: Key Differences

ABPA and CPA are fundamentally different disease processes caused by Aspergillus: ABPA is an allergic/hypersensitivity disorder occurring in asthmatic or cystic fibrosis patients, while CPA is a chronic infectious process that develops in pre-existing lung cavities or structural lung disease in non-immunocompromised patients. 1

Pathophysiology: The Core Distinction

ABPA is driven by an exaggerated type-2 immune response and hypersensitivity reaction to Aspergillus fumigatus antigens, with fungal persistence in the airways but without tissue invasion. 1, 2 The organism colonizes but does not invade lung tissue.

CPA represents a locally invasive chronic infection where Aspergillus species directly cause progressive cavity formation, expansion, and tissue destruction over months to years. 1 This is an infectious process, not primarily allergic.

Patient Population and Risk Factors

ABPA occurs in:

• Patients with moderate-to-severe asthma (prevalence ~13% in asthma clinics) 3
• Cystic fibrosis patients (approximately 7% develop ABPA) 4
• Patients with intact immune systems 5

CPA develops in:

• Patients with pre-existing structural lung disease: prior tuberculosis, non-tuberculous mycobacterial infection, COPD, treated lung cancer, prior pneumothorax 1
• Pre-formed lung cavities or bronchiectasis from any cause 1
• Fibrocystic sarcoidosis, ankylosing spondylitis, pneumoconiosis 1
• Critically: CPA can complicate advanced ABPA (ABPA-CPF subtype requires exclusion of CPA) 1

Clinical Presentation

ABPA presents with:

• Episodic wheezing, uncontrolled asthma, cough, dyspnea 6
• Expectoration of brown mucus plugs 4
• Fleeting pulmonary infiltrates 1, 6
• Symptoms of allergic inflammation (fever, malaise) 4

CPA presents with:

• Chronic respiratory symptoms lasting >3 months 7
• Progressive cavity formation and lung destruction 1
• Hemoptysis (sometimes life-threatening from pseudo-aneurysms) 1
• Weight loss, chronic cough, fatigue 7
• Aspergilloma (fungal ball) as a late manifestation 1

Immunological Markers: Critical Diagnostic Differences

ABPA requires:

• Markedly elevated total IgE ≥500 IU/mL (often >1000 IU/mL) 1, 6
• Elevated A. fumigatus-specific IgE (mandatory criterion) 1, 8, 6
• Peripheral blood eosinophilia ≥500 cells/μL 6
• A. fumigatus-specific IgG (supportive but not diagnostic alone) 8

CPA requires:

• Elevated Aspergillus IgG antibody or precipitins (positive in >90% of cases, cornerstone of diagnosis) 1, 7
• Total IgE may be elevated but is NOT a diagnostic criterion 1
• Aspergillus-specific IgE can be detectable in CPA patients but is not required 1
• Eosinophilia is NOT a feature of CPA 1

Key distinction: ABPA diagnosis centers on elevated IgE (both total and Aspergillus-specific), while CPA diagnosis relies on elevated IgG antibodies. 1, 8

Radiological Features

ABPA imaging shows:

• Central bronchiectasis (bilateral, upper/middle lobe predominant) 4, 6
• Mucus plugging (with or without high-attenuation mucus) 1
• High-attenuation mucus (pathognomonic when present) - mucus denser than paraspinal muscles on CT 1, 4
• Fleeting infiltrates, tree-in-bud nodules 1
• In advanced ABPA-CPF: fibrosis, fibro-cavitary lesions, fungal balls, pleural thickening 1

CPA imaging shows:

• Progressive cavity formation with or without fungal ball (aspergilloma) 1
• Cavity wall thickening, irregular bumpy interior cavity surface 1
• Upper lobe predominance with pleural thickening 1
• Marked parenchymal destruction and fibrosis 1
• "Air-crescent sign" around aspergilloma 1
• Enlargement of bronchial/systemic arteries 1

Critical caveat: When ABPA progresses to ABPA-CPF with cavities and fungal balls, CPA must be actively excluded as the two can coexist or CPA can complicate ABPA. 1 This requires careful correlation of immunological markers (IgE pattern vs. IgG predominance) and clinical context.

Treatment Approach: Fundamentally Different

ABPA treatment targets immune dysregulation:

• Glucocorticoids are first-line (prednisolone 0.5 mg/kg/day for 2-4 weeks, tapered over 4 months) 1
• Antifungal therapy (itraconazole) to reduce fungal burden 1
• Biologics targeting type-2 inflammation in refractory cases 1
• Goal: control immune response, prevent bronchiectasis progression 1

CPA treatment targets infection:

• Long-term oral azole antifungals (itraconazole or voriconazole for months to years) 7
• Surgery for well-circumscribed simple aspergillomas 7
• Intravenous amphotericin B or micafungin for azole-resistant/intolerant cases 7
• Goal: arrest infection, prevent cavity progression, control hemoptysis 1, 7

Diagnostic Algorithm Summary

For suspected ABPA: Check total IgE, A. fumigatus-specific IgE, blood eosinophil count, and thin-section chest CT looking for central bronchiectasis and high-attenuation mucus. 1, 4, 6

For suspected CPA: Check Aspergillus IgG antibody/precipitins and contrast-enhanced chest CT looking for cavities, fungal balls, and pleural thickening in patients with chronic lung disease. 1

Common pitfall: In patients with advanced ABPA showing cavities and fungal balls (ABPA-CPF), always exclude concurrent CPA by carefully evaluating the immunological profile and clinical trajectory. 1 The presence of very high IgE with eosinophilia favors ABPA, while predominant IgG elevation without marked IgE elevation or eosinophilia suggests CPA.