How is aspergilloma diagnosed and managed in patients with pre‑existing lung cavities such as post‑tuberculosis?

Aspergilloma: Diagnosis and Management in Post-Tuberculosis Cavities

In patients with post-tuberculosis lung cavities, aspergilloma should be diagnosed by demonstrating a fungal ball on CT imaging combined with positive Aspergillus-specific IgG antibodies (present in >90% of cases), and management depends critically on distinguishing simple aspergilloma (which warrants surgical resection when feasible) from chronic cavitary pulmonary aspergillosis (which requires long-term antifungal therapy). 1, 2

Diagnostic Approach

Clinical Context and Risk Factors

• Post-tuberculosis cavities are the predominant risk factor for aspergilloma development, along with other structural lung diseases including non-tuberculous mycobacterial infection, COPD, fibrocystic sarcoidosis, and prior pneumothorax 1
• The fungus colonizes pre-existing cavities as a saprophytic infection, forming a conglomeration of fungal hyphae, fibrin, mucus, and cellular debris 1, 3
• Symptoms range from asymptomatic incidental findings to life-threatening hemoptysis, with hemoptysis being the most common presenting symptom when present 1, 3

Imaging Findings

Obtain high-resolution CT with contrast (CT angiography) as the essential baseline imaging study 1

Key radiological features include:

• "Air-crescent" sign: solid, round or oval intracavitary mass partially surrounded by a crescent of air, typically mobile on prone positioning 1
• Upper-lobe predominance with the fungal ball appearing as water density within a spherical or ovoid cavity 1
• Adjacent pleural thickening is highly characteristic 1
• The fungal ball does not enhance after intravenous contrast administration 1
• Prior to mature aspergilloma formation, look for irregular or bumpy interior cavity surfaces representing mats of fungal growth 1
• Calcification may appear as flecks, dense nodules, or extensive deposits throughout the aspergilloma 1

Microbiological and Serological Confirmation

Aspergillus-specific IgG antibodies (precipitins) are the most sensitive diagnostic test, positive in >90% of chronic pulmonary aspergillosis cases 2

Additional confirmatory methods include:

• Strongly positive Aspergillus antigen or DNA in respiratory fluids 2
• Sputum culture positive for Aspergillus species (56-81% of cases), though isolation from sputum alone does not confirm infection due to ubiquitous colonization 2
• Bronchoscopic specimens are far more indicative of true disease than sputum alone 2
• Percutaneous or surgical biopsy showing fungal hyphae or culture from the cavity 2

Critical Differential Diagnosis

Always exclude active mycobacterial infection, as dual infections are frequent and associated with poorer outcomes 2, 4

Mandatory testing includes:

• Sputum smear for acid-fast bacilli, nucleic acid amplification, and mycobacterial culture 2
• Consider endemic fungal infections based on geography: chronic cavitary histoplasmosis, coccidioidomycosis, paracoccidioidomycosis 2
• Exclude necrotic lung carcinoma, which can mimic aspergilloma radiographically 1, 4
• Rule out other causes: pulmonary infarction, vasculitides, rheumatoid nodules 2

Classification: Simple vs. Complex Disease

Simple (Single) Aspergilloma

Defined by a single fungal ball in a single pulmonary cavity with minimal or no symptoms, no radiological progression over ≥3 months, and positive Aspergillus serology 1, 2

Chronic Cavitary Pulmonary Aspergillosis (CCPA)

Characterized by one or more cavities (possibly containing aspergillomas), significant pulmonary/systemic symptoms (cough, dyspnea, hemoptysis, weight loss, fatigue), and overt radiological progression over ≥3 months 1, 2

Progressive features include:

• New cavities, increasing pericavitary infiltrates, or increasing fibrosis 1
• Multiple expanding thick-walled cavities with concomitant pleural thickening 1
• Cavities enlarge and coalesce over months to years if untreated 1
• Enlargement of bronchial or systemic arteries with potential pseudo-aneurysms leading to fatal hemoptysis 1

The 3-month duration criterion is critical for distinguishing CCPA from subacute invasive aspergillosis (SAIA), which progresses over 1-3 months in moderately immunocompromised patients and requires aggressive invasive-aspergillosis treatment protocols 1, 2

Management Strategy

Simple Aspergilloma

Surgical resection (preferably video-assisted thoracic surgery) is the recommended treatment when the patient is a suitable operative candidate 1, 2

• Surgery is currently the mainstay but carries considerable mortality and morbidity, particularly in patients with impaired lung function 3, 5
• Antifungal therapy is reserved for incompletely resected lesions or multiple nodules 2
• Systemic azoles (itraconazole, voriconazole, posaconazole) provide therapeutic benefit with minimal risk for patients who are poor surgical candidates 1, 5
• Systemic amphotericin B monotherapy is ineffective and not recommended 5

Chronic Cavitary Pulmonary Aspergillosis (CCPA)

Long-term oral antifungal therapy is required to improve overall health, control respiratory symptoms, arrest hemoptysis, and prevent disease progression 2

First-line antifungal regimen:

• Voriconazole: loading dose 6 mg/kg IV every 12 hours × 2 doses, then maintenance 4 mg/kg IV every 12 hours or 200 mg orally twice daily 2
• Itraconazole is an accepted alternative for prolonged treatment 1, 2
• Posaconazole is a presumed effective alternative based on mechanism 1

Treatment duration and monitoring:

• Minimum initial treatment duration is 4-6 months, extending to ≥9 months if response is limited 2
• Indefinite suppressive therapy may be required for persistent CCPA 1, 2
• Therapeutic drug monitoring of azole serum concentrations is essential due to variable bioavailability and frequent toxicity 2
• Monitor for drug interactions, especially rifampicin (used for concurrent TB), requiring dose adjustments 2
• Regular assessment for azole-related toxicities: hepatic, visual, dermatologic 2

Hemoptysis Management

New or worsening hemoptysis may indicate therapeutic failure or antifungal resistance 2

Management hierarchy:

1. Oral tranexamic acid for mild-moderate bleeding 2
2. Bronchial artery embolization for severe hemoptysis 2, 5
3. Surgical resection only for localized disease refractory to other measures 2
4. Radiotherapy as an option to manage hemoptysis until definitive eradication 5

Alternative Non-Surgical Options

For inoperable patients or those preferring less invasive approaches:

• Intracavitary instillation or endobronchial administration of antifungal medication 5
• Direct transbronchial aspergilloma removal 5
• Systemic azoles effective in approximately 50-80% of patients 5

Common Pitfalls and Caveats

• Do not base CPA diagnosis solely on positive sputum culture, as Aspergillus colonization is common in damaged lungs 2
• Always obtain mycobacterial studies in cavitary lung disease to avoid missing concurrent infection, which is frequent and worsens outcomes 2
• Do not apply the 3-month duration criterion loosely: symptom progression within 1-3 months suggests SAIA and warrants invasive-aspergillosis treatment protocols rather than chronic disease management 2
• Therapeutic drug monitoring for azoles must not be omitted because of variable bioavailability and frequent toxicity 2
• In patients with rheumatoid disease, pulmonary rheumatoid nodules may cavitate and become colonized by Aspergillus, creating mixed lesions 4
• Follow-up imaging should use low-dose CT or chest radiographs to minimize cumulative radiation exposure 1
• Repeat imaging at 3 or 6 months or with change of clinical status 1