What are the diagnostic criteria for Chronic Pulmonary Aspergillosis (CPA) in a patient with a history of pulmonary disease, such as tuberculosis or Chronic Obstructive Pulmonary Disease (COPD)?

Diagnostic Criteria for Chronic Pulmonary Aspergillosis (CPA)

The diagnosis of CPA requires three essential components present for at least 3 months: characteristic thoracic imaging findings (preferably by CT scan), direct or immunological evidence of Aspergillus infection, and exclusion of alternative diagnoses, occurring in patients who are not severely immunocompromised. 1

Core Diagnostic Requirements

Temporal Criterion

• Disease duration of at least 3 months is mandatory, even if inferred from symptoms or progressive radiological changes 1, 2
• This 3-month threshold distinguishes CPA from subacute invasive aspergillosis (SAIA), which progresses over 1-3 months in mildly immunocompromised patients 1, 2

Patient Population

• Patients must be non-immunocompromised or only mildly immunocompromised (arbitrarily defined as ≤10 mg prednisolone daily or equivalent) 1
• CPA typically develops in patients with pre-existing structural lung disease including tuberculosis, COPD, NTM infection, ABPA, sarcoidosis, prior pneumothorax, or treated lung cancer 1, 2

Imaging Criteria

Required Radiological Features

CT scan with intravenous contrast is the gold standard imaging modality (Strength of Recommendation A, Quality of Evidence II) 1

The characteristic imaging findings include:

• One or more pulmonary cavities (thin or thick-walled) with or without fungal balls 1
• New and/or expanding cavities of variable wall thickness 1
• Intracavitary fungal ball formation (aspergilloma) showing the classic "air-crescent sign" 1
• Pleural thickening, often adjacent to cavities 1
• Upper lobe fibrosis and marked parenchymal destruction 1
• Irregular interior cavity surface ("bumpy" appearance) representing fungal mat growth prior to aspergilloma formation 1

Chest radiographs are acceptable for initial suspicion but have limited sensitivity compared to CT 1, 3

PET scanning is not useful as aspergillosis causes false-positive results (Strength of Recommendation D, Quality of Evidence III) 1

Microbiological/Immunological Evidence

For Fungal Ball (Simple Aspergilloma)

If a fungal ball is visualized on imaging, only positive Aspergillus IgG or precipitins testing is required (positive in >90% of cases) 1, 2

For Cavitary Disease Without Fungal Ball

Any ONE of the following confirms the diagnosis after excluding alternative diagnoses 1:

Serological Testing (First-Line)

• Aspergillus IgG antibody (Strength of Recommendation A, Quality of Evidence II) - sensitivity >90% 1, 3
• Aspergillus precipitins (Strength of Recommendation A, Quality of Evidence II) - though sensitivity is uncertain 1
• Aspergillus IgE antibody (Strength of Recommendation B, Quality of Evidence II) - particularly in patients with asthma, ABPA, or cystic fibrosis 1

Direct Evidence

• Strongly positive Aspergillus galactomannan antigen in respiratory fluids (optimal cut-off ≥0.69 in BAL) 1, 4
• Aspergillus DNA detection in respiratory specimens 1
• Percutaneous or excision biopsy showing fungal hyphae on microscopy or growing Aspergillus species from a cavity 1
• Culture of Aspergillus species from respiratory specimens on fungal media 3

Important Caveat on Serology

Aspergillus serology is typically negative in invasive aspergillosis, making it useful for distinguishing CPA from invasive disease 2

Clinical Criteria

Symptom Requirements Vary by CPA Subtype

Simple Aspergilloma:

• Single cavity with fungal ball 1, 2
• Minimal or no symptoms 1, 2
• No radiological progression over at least 3 months 1, 2

Chronic Cavitary Pulmonary Aspergillosis (CCPA):

• One or more cavities (most common form) 1, 2
• Significant pulmonary symptoms (productive cough, hemoptysis) and/or systemic symptoms (weight loss, fatigue, fever) 1, 2, 5
• Overt radiological progression (new cavities, increasing pericavitary infiltrates, or increasing fibrosis) over at least 3 months 1, 2

Chronic Fibrosing Pulmonary Aspergillosis (CFPA):

• Severe fibrotic destruction of at least two lobes leading to major loss of lung function 1, 2

Exclusion of Alternative Diagnoses

Critical differential diagnoses that must be excluded include 5:

• Mycobacterial infection (tuberculosis or NTM) - particularly important in TB-endemic areas where CPA is frequently misdiagnosed as smear-negative pulmonary TB 6, 5
• Bacterial lung abscess or necrotizing pneumonia 5
• Lung cancer 5
• Endemic fungi 5

In TB-endemic settings, repeat sputum GeneXpert assays should be negative before diagnosing CPA 6

Common Diagnostic Pitfalls

• CPA is often missed for years and patients are mismanaged, emphasizing the need for radiological reports to mention possible CPA when characteristic features are present 1
• The 3-month duration criterion is critical: symptoms present for <3 months suggest SAIA or invasive disease requiring more aggressive management 2
• Sputum culture lacks sensitivity for Aspergillus, making serology the cornerstone of diagnosis 5
• BAL-PCR and BAL-galactomannan have suboptimal sensitivity (52% and 47% respectively) and should not be used as sole "rule-in" tests 4
• Patients may have concurrent CPA and other infections (e.g., mycobacterial disease), requiring careful evaluation 1