What are the diagnostic criteria and treatment options for a patient suspected of having Chronic Pulmonary Aspergillosis (CPA) with underlying lung disease and potential immunocompromised state?

Diagnostic Criteria for Chronic Pulmonary Aspergillosis

The diagnosis of CPA requires three essential components present for at least 3 months: characteristic thoracic imaging findings (preferably CT scan), direct evidence of Aspergillus infection or immunological response to Aspergillus species, and exclusion of alternative diagnoses. 1

Core Diagnostic Requirements

1. Duration Criterion

• Symptoms or radiological abnormalities must be present for at least 3 months to distinguish CPA from acute or subacute invasive aspergillosis 1, 2
• This duration may be inferred based on progressive radiological changes or chronic symptoms 1

2. Imaging Findings (CT Scan Strongly Recommended)

Obtain a contrast-enhanced CT scan (CT angiography) as the primary diagnostic imaging modality for all suspected CPA cases 1

Key radiological features include:

• One or more cavities with variable wall thickness, with or without intracavitary fungal ball formation 1
• Fungal ball (aspergilloma): solid, round or oval intracavitary mass with surrounding air-crescent sign, mobile with prone positioning 1
• Pleural thickening adjacent to affected areas 1
• Upper lobe predominance with fibrosis and parenchymal destruction 1
• New or expanding cavities in the setting of chronic lung disease 1
• Irregular "bumpy" interior cavity surface representing fungal mat growth prior to aspergilloma formation 1

Important caveat: Chest radiographs have limited sensitivity and should not be relied upon alone; CT provides superior definition of abnormalities 1, 3

3. Microbiological/Immunological Evidence

For patients with visible fungal ball on imaging:

• Aspergillus IgG antibody or precipitins test is sufficient if positive (positive in >90% of cases) 1

For patients with cavities without visible fungal ball, ANY of the following confirms diagnosis:

• Positive Aspergillus IgG antibody (Strength of Recommendation A, Quality of Evidence II) 1
• Positive Aspergillus precipitins (Strength of Recommendation A, Quality of Evidence II) 1
• Strongly positive Aspergillus antigen or DNA in respiratory fluids 1
• Biopsy (percutaneous or excision) showing fungal hyphae on microscopy or growing Aspergillus species from cavity 1
• Respiratory samples showing hyphae consistent with Aspergillus and/or growing Aspergillus species support but are insufficient alone for confirmed diagnosis 1

Critical distinction: If hyphae are seen invading lung parenchyma on biopsy, the diagnosis is acute or subacute invasive aspergillosis, not CPA 1

4. Patient Population Characteristics

• Patients are typically not severely immunocompromised (no HIV-related immunosuppression, cancer chemotherapy, or high-dose immunosuppressive therapy) 1
• Arbitrary cut-off: ≤10 mg prednisolone daily (or equivalent) for clinical management of CPA 1
• Underlying structural lung disease is almost always present 1, 4, 2

Common Underlying Conditions to Identify

The following pre-existing lung diseases are major risk factors 1:

• Prior tuberculosis (most common) 1, 2
• Non-tuberculous mycobacterial (NTM) infection 1
• Allergic bronchopulmonary aspergillosis (ABPA) 1
• COPD 1
• Bronchiectasis 1
• Prior pneumothorax or treated lung cancer 1
• Fibrocystic sarcoidosis 1
• Pneumoconiosis and progressive massive fibrosis in silicosis 1

Exclusion of Alternative Diagnoses

Must actively exclude the following before confirming CPA diagnosis:

Mycobacterial Infections

• Perform sputum smear, mycobacterial nucleic acid amplification, and culture to exclude pulmonary tuberculosis or NTM infection 4
• Important: CPA and mycobacterial disease can occur simultaneously 4, 2

Other Fungal Infections

• Consider chronic cavitary histoplasmosis, paracoccidioidomycosis, and coccidioidomycosis based on geographic exposure 4
• Require specific antibody/antigen detection and respiratory cultures 4

Non-infectious Causes

• Necrotizing lung cancer 4
• Pulmonary infarction 4
• Vasculitides 4
• Rheumatoid nodules 4

Diagnostic Algorithm

1. Identify characteristic imaging: Obtain contrast-enhanced CT showing cavities, fungal balls, pleural thickening, or upper lobe fibrosis 1

2. Confirm ≥3-month duration: Document chronic symptoms (cough, hemoptysis, weight loss, dyspnea) or progressive radiological changes over at least 3 months 1, 4

3. Obtain Aspergillus serology: Order Aspergillus IgG antibody or precipitins test (positive in >90% of CPA cases) 1, 2

4. If serology negative or equivocal: Perform bronchoscopy with bronchoalveolar lavage for galactomannan testing, culture, and microscopy 3

5. Exclude alternative diagnoses: Send sputum for mycobacterial smear and culture; consider biopsy if malignancy suspected 4

6. Assess immune status: Verify patient is not severely immunocompromised (≤10 mg prednisolone daily or equivalent) 1

Common Diagnostic Pitfalls

• CPA is frequently missed for years and patients are mismanaged; radiological reports must explicitly mention possible CPA when characteristic features are present 1
• PET scans are not useful for CPA diagnosis as aspergillosis causes false-positive results mimicking malignancy (Strength of Recommendation D) 1
• Aspergillus IgM and IgA antibodies have insufficient data and should not be used for diagnosis (Strength of Recommendation D) 1
• BALF galactomannan and PCR have suboptimal sensitivity/specificity and should not be used as sole "rule-in" tests 5
• Serum galactomannan has lower sensitivity (30%) compared to Aspergillus IgG antibody for CPA diagnosis 6