What are the diagnostic criteria and treatment options for pulmonary aspergillosis in an immunocompromised patient?

How to Recognize Pulmonary Aspergillosis

The diagnosis of pulmonary aspergillosis requires a combination of characteristic imaging findings (cavities, nodules, or fungal balls on CT scan), microbiological or immunological evidence of Aspergillus infection (positive Aspergillus IgG antibody in >90% of cases), and symptoms or radiological progression present for at least 3 months, with exclusion of alternative diagnoses. 1

Clinical Presentation by Disease Type

Chronic Cavitary Pulmonary Aspergillosis (CCPA)

• Pulmonary symptoms: Chronic cough, dyspnea, hemoptysis, and weight loss occurring over at least 3 months 1
• Systemic symptoms: Fatigue, malaise, and fever may be present 1
• Patient population: Non-immunocompromised patients with underlying lung disease (prior tuberculosis, COPD, bronchiectasis, sarcoidosis) 1
• Radiological progression: New cavities, increasing pericavitary infiltrates, or increasing fibrosis over at least 3 months 1

Simple Aspergilloma

• Minimal or no symptoms: Very few pulmonary or systemic symptoms 1
• Imaging finding: Single fungal ball in a single pulmonary cavity 1
• No progression: Stable appearance over at least 3 months of observation 1

Subacute Invasive Aspergillosis (SAIA)

• Rapid progression: Symptoms develop over 1-3 months, faster than CCPA 1
• Patient population: Mildly immunocompromised patients (diabetes mellitus, malnutrition, alcoholism, prolonged corticosteroids >10 mg prednisolone daily, chronic lung disease, HIV infection) 1
• More severe presentation: Progressive consolidation, cavitation with irregular walls, and systemic symptoms 1

Diagnostic Imaging Criteria

CT Scan Findings (Essential for Diagnosis)

• Cavitary lesions: One or more pulmonary cavities with thin or thick walls 1
• Fungal ball (aspergilloma): Spherical mass within a cavity, often with air crescent sign, representing collapsed fungal growth 1
• Irregular intraluminal material: Surface growth of Aspergillus on cavity interior walls 1
• Progressive changes: New cavities, increasing pericavitary infiltrates, pleural thickening, or fibrosis on serial imaging 1, 2
• Nodules: Single or multiple nodules that may cavitate (Aspergillus nodule form) 1, 2

Chest X-ray Limitations

• Aspergillomas appear as spherical-shaped objects, but CT is superior for characterization 3
• Less sensitive than CT for detecting early disease or subtle progression 2

Microbiological and Immunological Confirmation

Aspergillus IgG Antibody (Precipitins) - Primary Diagnostic Test

• Positive in >90% of CPA cases, making it the most sensitive test 1, 4
• Sufficient for diagnosis when fungal ball is visible on imaging 1
• Strongly recommended as first-line serological test 4

Respiratory Sample Analysis

• Sputum or bronchoscopic culture: Aspergillus fumigatus isolated in 56-81% of cases 1
• Microscopy: May reveal fungal hyphae, though not systematically validated 1
• PCR assay: Positive Aspergillus DNA supports diagnosis but is insufficient alone 1
• Important caveat: Aspergillus in sputum alone is not diagnostic due to ubiquitous nature; bronchoscopic specimens are more specific for infection versus colonization 1

Additional Confirmatory Tests (When Antibody Negative)

• Strongly positive Aspergillus galactomannan antigen in respiratory fluids or blood (more common in SAIA) 1
• Percutaneous or excision biopsy: Showing fungal hyphae on microscopy or growing Aspergillus from cavity tissue 1
• Histological invasion: If hyphae invade lung parenchyma, diagnosis shifts to acute or subacute invasive aspergillosis 1

Differential Diagnosis - Critical Exclusions

Mycobacterial Infection (Most Common Differential)

• Pulmonary tuberculosis or non-tuberculous mycobacterial infection may precede, follow, or occur simultaneously with CPA 1
• Required workup: Sputum smear, mycobacterial nucleic acid amplification, and culture 1
• Important note: Diagnosing mycobacterial infection does not exclude CPA 1

Other Fungal Infections (Geographic Considerations)

• Chronic cavitary histoplasmosis, paracoccidioidomycosis, coccidioidomycosis present similarly 1
• Distinguished by specific antibody/antigen detection and respiratory cultures 1

Non-Infectious Causes

• Necrotizing lung cancer: Especially with thick cavity walls, older age, smoking history 1, 2
• Pulmonary infarction, vasculitides, rheumatoid nodules 1, 2

Bacterial Superinfection

• Cavities may be infected with Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, or anaerobes 1
• These require treatment but do not negate CPA diagnosis 1

Diagnostic Algorithm

Step 1: Identify Characteristic Imaging

• Obtain chest CT with thin sections (1.5 mm) to characterize cavities, fungal balls, nodules, or progressive infiltrates 2
• Document duration of symptoms or radiological abnormalities ≥3 months 1

Step 2: Confirm Aspergillus Involvement

• If fungal ball present: Aspergillus IgG antibody test alone is sufficient 1
• If cavities without fungal ball: Obtain Aspergillus IgG antibody, respiratory cultures (sputum or bronchoscopy), and consider galactomannan or PCR 1
• If antibody negative: Pursue biopsy showing fungal hyphae or strongly positive antigen/DNA in respiratory fluids 1

Step 3: Exclude Alternative Diagnoses

• Send respiratory samples for mycobacterial smear, nucleic acid amplification, and culture 1
• Consider bacterial cultures if acute symptoms suggest superinfection 1
• Evaluate for malignancy if thick-walled cavity in smoker or older patient 2

Step 4: Classify Disease Type

• Simple aspergilloma: Single cavity, single fungal ball, minimal symptoms, no progression 1
• CCPA: Multiple cavities or progressive disease with significant symptoms 1
• SAIA: Rapid progression (<3 months) in mildly immunocompromised patient, often with positive serum galactomannan 1

Common Pitfalls to Avoid

• Do not dismiss Aspergillus in sputum as mere colonization when cavitary disease is present; bronchoscopic isolation strongly suggests infection 1
• Do not rely on single negative culture; multiple respiratory samples increase diagnostic yield 1
• Do not assume mycobacterial infection excludes CPA; both can coexist and require concurrent treatment 1, 4
• Do not overlook SAIA in patients on modest immunosuppression (e.g., >10 mg prednisolone daily, diabetes, malnutrition); these patients may have detectable antibody and antigen simultaneously 1
• Do not use bacterial culture media alone; fungal-specific media increase Aspergillus recovery rates 1