Risk Factors for Allergic Bronchopulmonary Aspergillosis (ABPA)
The primary risk factors for ABPA are asthma and cystic fibrosis, with genetic predisposition playing a significant role in determining which patients with these conditions develop ABPA. 1
Major Predisposing Conditions
Respiratory Disorders
- Asthma: Most common predisposing condition, with ABPA occurring in 7-14% of corticosteroid-dependent asthmatics 1
- Cystic Fibrosis (CF): Approximately 7-9% of CF patients develop ABPA 2
- CFTR mutations: Even in patients without classic CF, CFTR gene variants can predispose to ABPA 3, 2
- Bronchiectasis: Can be both a cause and consequence of ABPA 4
- COPD: Less common but recognized predisposing condition 1
Genetic Factors
- HLA associations: Specific HLA-DR2 and HLA-DR5 haplotypes increase susceptibility 5
- IL-4 receptor alpha chain polymorphisms: Affect Th2 immune responses 2
- IL-10 promoter polymorphisms: Influence inflammatory regulation 2
- Surfactant protein A2 (SP-A2) polymorphisms: Affect innate immunity 2
Immunological Factors
- Atopy: General predisposition to allergic responses 2
- Th2-skewed immune responses: Heightened responses to Aspergillus antigens 2, 6
- Impaired mucociliary clearance: Common in both asthma and CF 6
Environmental and Microbiological Factors
- Airway colonization with Aspergillus fumigatus: Most common causative organism 1
- Repeated exposure to Aspergillus spores: Environmental exposure is necessary but not sufficient 7
- Persistent fungal growth in airways: Particularly in patients with mucus plugging 6
Disease Progression Risk Factors
- Delayed diagnosis: Increases risk of progression to bronchiectasis 4
- Recurrent exacerbations: Associated with worse outcomes 4
- Inadequate treatment: Particularly insufficient corticosteroid therapy 1
- High fungal burden: Associated with more severe disease 1
Clinical Presentation Risk Factors
- Mucus plugging: Characteristic finding that increases risk of bronchiectasis 1
- High-attenuation mucus (HAM): Associated with more severe disease 1
- Central bronchiectasis: Classic radiological finding associated with ABPA 4
- Elevated total IgE (>500 IU/mL): Key diagnostic marker and risk factor 1
- Peripheral blood eosinophilia: Common finding in ABPA patients 1
Clinical Implications
- Patients with asthma or CF should be screened for Aspergillus sensitization, particularly those with difficult-to-control disease 1
- Early identification and treatment are crucial to prevent progression to bronchiectasis 1, 4
- Genetic testing may be warranted in patients with ABPA to identify underlying CFTR mutations, especially with atypical presentations 3
- Regular monitoring of total IgE levels helps assess disease activity and response to therapy 1, 4
Understanding these risk factors is essential for early identification of at-risk patients and timely intervention to prevent the development of permanent lung damage from ABPA.