What are the diagnostic criteria for Chronic Pulmonary Aspergillosis (CPA) in a patient with chronic pulmonary symptoms and a history of chronic pulmonary disease or immunocompromised states?

Diagnostic Criteria for Chronic Pulmonary Aspergillosis

The diagnosis of CPA requires three essential components present for at least 3 months: (1) characteristic thoracic imaging findings on CT scan showing cavitation, pleural thickening, pericavitary infiltrates, or fungal ball; (2) direct microbiological evidence of Aspergillus infection or positive Aspergillus IgG antibody; and (3) exclusion of alternative diagnoses, all in a patient with minimal or no immunocompromise. 1

Core Diagnostic Requirements

Temporal Criterion

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

Immune Status

• Patients must have no or minimal immunocompromise 1
• An arbitrary cutoff of ≤10 mg prednisolone daily (or equivalent) is recommended for clinical management 1
• Patients with HIV infection, active cancer chemotherapy, or significant immunosuppressive therapy are typically excluded from the CPA diagnosis 1

Radiological Criteria

Imaging Modality

• CT scan with contrast (CT-angiography) is the preferred imaging modality and should be obtained at baseline 1
• Chest radiographs can raise initial suspicion but lack the sensitivity and specificity of CT 1

Characteristic Findings

• One or more pulmonary cavities with thin or thick walls, possibly containing aspergillomas or irregular intraluminal material 1
• Pleural thickening, often bilateral and accentuated by adjacent hypertrophied extrapleural fat 1
• Pericavitary infiltrates representing surface growth of Aspergillus on cavity walls 1
• Progressive radiological changes including new cavities, increasing infiltrates, or advancing fibrosis over time 1
• Fungal balls (aspergillomas) may be present but are not required for diagnosis 1

Microbiological and Serological Criteria

For Fungal Ball (Aspergilloma)

• Positive Aspergillus IgG antibody or precipitins test alone is sufficient when a fungal ball is visualized on imaging 1
• This test is positive in >90% of cases with aspergilloma 1

For Cavitary Disease Without Fungal Ball

Any of the following confirms the diagnosis after excluding alternative conditions 1:

• Positive Aspergillus IgG or precipitins (most sensitive microbiological test) 1
• Strongly positive Aspergillus antigen in respiratory fluids 1
• Positive Aspergillus DNA (PCR) in respiratory fluids (more sensitive than culture) 1
• Percutaneous or excision biopsy showing fungal hyphae on microscopy or growing Aspergillus species from a cavity 1
• Respiratory samples showing hyphae consistent with Aspergillus and/or growing Aspergillus species support but do not alone confirm diagnosis 1

Critical Distinction

• If hyphae are seen invading lung parenchyma on biopsy, the diagnosis is acute or subacute invasive aspergillosis, not CPA 1
• Patients with detectable Aspergillus galactomannan antigen in blood are more likely to have SAIA rather than CPA 1

Clinical Context

Underlying Conditions

CPA typically develops in patients with pre-existing structural lung disease 1:

• Previous tuberculosis or non-tuberculous mycobacterial infection (most common, ~30% combined) 3
• Allergic bronchopulmonary aspergillosis (ABPA) 4, 3
• Chronic obstructive pulmonary disease (COPD) or emphysema 1, 3
• Prior pneumothorax or treated lung cancer 3
• Bronchiectasis, sarcoidosis, connective tissue disorders, or radiation therapy 1

Symptoms

• Chronic pulmonary symptoms including productive cough, hemoptysis, dyspnea, chest pain 1
• Systemic symptoms such as weight loss, fatigue, fever, night sweats 1
• Symptoms must be present or progressive for at least 3 months 1

Differential Diagnosis to Exclude

The following must be ruled out before confirming CPA 1:

• Active tuberculosis or non-tuberculous mycobacterial infection (sputum culture, PCR)
• Bacterial lung abscess or necrotizing pneumonia (clinical course, cultures)
• Lung cancer (biopsy if indicated)
• Endemic fungi (histoplasmosis, coccidioidomycosis in appropriate geographic areas)
• Other cavitary lung diseases (Wegener's granulomatosis, rheumatoid nodules)

Specific CPA Subtypes

Simple Aspergilloma

• Single pulmonary cavity containing a fungal ball 1
• Minor or no symptoms and no radiological progression over at least 3 months 1
• Positive Aspergillus serology 1

Chronic Cavitary Pulmonary Aspergillosis (CCPA)

• One or more cavities with or without aspergillomas 1, 2
• Significant pulmonary and/or systemic symptoms 1, 2
• Overt radiological progression (new cavities, increasing infiltrates, advancing fibrosis) over at least 3 months 1, 2

Chronic Fibrosing Pulmonary Aspergillosis (CFPA)

• Severe fibrotic destruction of at least two lobes complicating CCPA 1, 2
• Major loss of lung function 1, 2

Common Pitfalls

• Missing the diagnosis due to low clinical suspicion in patients with chronic lung disease and upper lobe cavitary changes 1, 5
• Misdiagnosing CPA as tuberculosis, particularly in low- and middle-income countries 6
• Failing to obtain Aspergillus serology, which is the most sensitive test and should be performed in all suspected cases 1
• Interpreting positive sputum culture alone as diagnostic when it merely supports but does not confirm CPA 1
• Not recognizing that tissue invasion on biopsy excludes CPA and indicates invasive or subacute invasive aspergillosis requiring different management 1
• Overlooking the 3-month duration requirement, which is essential for distinguishing CPA from more acute forms of aspergillosis 1, 2