What are the current guideline‑based management recommendations for allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and invasive pulmonary aspergillosis (IPA)?

Pulmonary Aspergillosis Management Guidelines

The management of pulmonary aspergillosis requires distinct treatment approaches based on the specific clinical form: invasive pulmonary aspergillosis (IPA) demands immediate voriconazole or isavuconazole; chronic pulmonary aspergillosis (CPA) requires oral azoles for at least 6 months; and allergic bronchopulmonary aspergillosis (ABPA) responds best to low-to-moderate dose oral prednisolone (0.5 mg/kg/day tapered over 4 months) with or without antifungal therapy. 1, 2

Invasive Pulmonary Aspergillosis (IPA)

First-Line Treatment

• Voriconazole is the preferred first-line agent with a loading dose of 6 mg/kg IV every 12 hours for 24 hours, then 4 mg/kg IV every 12 hours. 2
• Isavuconazole and posaconazole are equally effective first-line alternatives, particularly in patients with renal impairment or those requiring oral therapy. 3
• Treatment should be initiated immediately in strongly suspected cases to prevent mortality, even while diagnostic evaluation proceeds. 2

Alternative Agents

• Echinocandins (caspofungin, micafungin, anidulafungin) and amphotericin B formulations serve as second-line options when triazoles fail, are not tolerated, or resistance is documented. 3

Treatment Duration

• Continue antifungal therapy for at least 6-12 weeks, with duration determined by clinical response, radiological improvement, and elimination of risk factors. 3

Monitoring Requirements

• Therapeutic drug monitoring is essential for all azoles due to drug interactions and variable pharmacokinetics, especially in geriatric patients. 2
• Repeat imaging and clinical assessment every 3-6 months to detect treatment failure or resistance. 2

Chronic Pulmonary Aspergillosis (CPA)

Diagnostic Criteria

• CPA requires three key elements: chronic pulmonary symptoms lasting ≥3 months, characteristic radiological findings (cavitation, fungal ball, pleural thickening, or progressive fibrosis), and microbiological or serological evidence of Aspergillus. 1, 4
• Aspergillus-specific IgG antibody testing has 95.6% sensitivity and 100% specificity and is the most sensitive microbiological test available. 5, 4

Imaging Approach

• Contrast-enhanced chest CT is mandatory at baseline to assess cavitation, pleural thickening, pericavitary infiltrates, and fungal balls. 1, 5
• High-quality CT with vessel visualization is required; low-dose CT is acceptable for follow-up to minimize radiation exposure. 1
• PET scanning is not useful and should not be performed, as aspergillosis causes false-positive results. 1

Medical Management

• Oral itraconazole solution or voriconazole tablets are first-line treatments for symptomatic CPA with hemoptysis, weight loss, or progressive lung function decline. 1, 5, 2
• Isavuconazole capsules or posaconazole enteric-coated tablets serve as alternatives. 3
• Treatment duration must be at least 6 months for CPA, and at least 9 months for chronic cavitary pulmonary aspergillosis (CCPA). 3
• Therapeutic drug monitoring is required for all azole antifungals. 1

Surgical Considerations

• Single aspergilloma with significant hemoptysis should be surgically resected if the patient is fit for surgery (no contraindications, adequate pulmonary reserve). 1, 2
• Surgery is indicated for localized disease unresponsive to medical therapy, pan-azole-resistant Aspergillus fumigatus, or persistent hemoptysis despite bronchial artery embolization. 5, 2
• Complex aspergilloma (multicavity disease) has poor surgical outcomes and should be managed medically. 1

Hemoptysis Management Algorithm

1. Start oral tranexamic acid for acute bleeding episodes. 5
2. Proceed to bronchial artery embolization if medical management fails. 5
3. Consider surgical resection for persistent hemoptysis despite embolization in surgical candidates. 5
4. For non-surgical candidates with cavities communicating with bronchi, consider nebulized amphotericin B or intracavitary injection of amphotericin B or azoles. 3

Special Situation: CPA Complicating Tuberculosis

• Simultaneous treatment with standard four-drug anti-tuberculosis therapy plus oral azole antifungal therapy for a minimum of 6 months is required in patients with extensive pulmonary tuberculosis and aspergilloma. 5
• Monitor closely for drug-drug interactions between rifampin and azole antifungals, as rifampin significantly reduces azole levels. 5

Allergic Bronchopulmonary Aspergillosis (ABPA)

Diagnostic Criteria

• ABPA requires: (1) predisposing condition (asthma, cystic fibrosis, or bronchiectasis), (2) elevated total IgE ≥500 IU/mL (≥1000 IU/mL is less sensitive), (3) elevated Aspergillus-specific IgE, and (4) elevated Aspergillus-specific IgG. 1
• Skin testing is inferior to serum Aspergillus-specific IgE assay and is not required. 1

Radiological Classification

• ABPA-S (serological): No bronchiectasis on imaging. 1
• ABPA-B (bronchiectasis): Radiological evidence of bronchiectasis. 1
• ABPA-MP (mucus plugging): Mucus plugging without high-attenuation mucus. 1
• ABPA-HAM (high-attenuation mucus): High-attenuation mucus plugs visible on mediastinal windows. 1
• ABPA-CPF (chronic pleuropulmonary fibrosis): Two or more of: pulmonary fibrosis, fibro-cavitary lesions, fungal ball, pleural thickening. Chronic pulmonary aspergillosis must be excluded in this category. 1

Treatment for Acute ABPA

• Low-to-moderate dose oral prednisolone (0.5 mg/kg/day for 2-4 weeks, then tapered and completed over 4 months) is the most effective treatment for acute ABPA. 1
• This regimen produces similar exacerbation rates with fewer adverse events compared to higher-dose, longer-duration protocols. 1

Antifungal Therapy in ABPA

• Oral itraconazole solution is the most commonly used antifungal, but voriconazole, isavuconazole, and posaconazole are also effective. 1, 3
• The general course of antifungal therapy is 3-6 months. 3
• Antifungal therapy should not be routinely initiated in patients with Aspergillus sensitization alone (without meeting full ABPA criteria). 3

Glucocorticoid Use in COPD with Aspergillosis

• In COPD patients with secondary IPA or subacute invasive aspergillosis, glucocorticoid use should be minimized or avoided. 3
• For COPD with concomitant CPA experiencing exacerbations with wheezing, short-term, low-dose glucocorticoids may be considered alongside antifungal treatment. 3
• Avoid systemic glucocorticoids and long-term or high-dose inhaled corticosteroids in stable COPD patients with concomitant CPA. 3

Critical Pitfalls to Avoid

Diagnostic Errors

• Never rely solely on sputum culture, as sensitivity is limited; always obtain Aspergillus-specific IgG antibody testing. 4
• Do not assume a negative Aspergillus IgG excludes aspergilloma in patients receiving systemic corticosteroids, as serology may be falsely negative. 4
• Distinguish simple aspergilloma from CCPA: CCPA involves multiple cavities, progressive symptoms, and systemic inflammation over ≥3 months. 4

Treatment Errors

• Do not observe without treatment in patients with symptoms or hemoptysis; initiate antifungal therapy promptly. 2
• Do not delay antifungal therapy while awaiting additional microbiological confirmation if Aspergillus IgG is elevated and imaging is consistent. 2
• Never assume hemoptysis represents residual tuberculosis alone in patients with prior TB; always evaluate for aspergilloma. 5
• Do not use amphotericin B as first-line therapy unless oral agents fail or resistance develops. 5

Monitoring Errors

• Rising Aspergillus IgG titers indicate therapeutic failure or relapse; repeat testing before changing therapy to exclude laboratory error. 2
• Antibody titers do not correlate with disease extent or severity, so do not use them to gauge treatment response; use clinical and radiological criteria instead. 1