When should allergic bronchopulmonary aspergillosis (ABPA) be suspected in an adult with asthma or cystic fibrosis who has recurrent poorly controlled respiratory symptoms, new or worsening wheezing, cough with thick brown mucus plugs, frequent exacerbations, markedly elevated total serum IgE, peripheral eosinophilia, and radiologic findings such as fleeting infiltrates or central bronchiectasis?

When to Suspect Allergic Bronchopulmonary Aspergillosis (ABPA)

Suspect ABPA in any patient with asthma or cystic fibrosis who has difficult-to-control respiratory symptoms, particularly when accompanied by markedly elevated total serum IgE (≥500 IU/mL), peripheral eosinophilia, and characteristic radiologic findings such as fleeting infiltrates, mucus plugging, or central bronchiectasis. 1

High-Risk Patient Populations Requiring Heightened Suspicion

Asthma Patients

• Corticosteroid-dependent asthmatics warrant particular attention, as ABPA occurs in 7-14% of this population 1
• Patients with persistent or difficult-to-treat asthma despite optimal management should be screened 1
• The European Respiratory Society recommends screening all newly diagnosed asthmatic adults at tertiary care centers for A. fumigatus sensitization using fungus-specific IgE 1

Cystic Fibrosis Patients

• Approximately 7% of CF patients with airway colonization by Aspergillus species develop ABPA 1
• These patients face particularly high risk for invasive aspergillosis if lung transplantation is performed 1

Other At-Risk Populations

• Patients with non-CF bronchiectasis or COPD may develop ABPA 1
• ABPA can occasionally occur in the absence of any predisposing condition 1

Cardinal Clinical Features That Should Trigger Suspicion

Respiratory Symptoms

• Recurrent or poorly controlled wheezing despite standard asthma therapy 1
• Episodic bronchial obstruction with acute exacerbations 1
• Cough productive of thick, tenacious mucus plugs—particularly brown or greenish plugs or flecks 1, 2
• Progressive dyspnea unresponsive to bronchodilators 1
• Recurrent exacerbations (≥2 episodes) despite optimal asthma management 1

Laboratory Abnormalities

• Markedly elevated total serum IgE ≥500 IU/mL is mandatory for diagnosis 1
• Peripheral blood eosinophilia (often >1000 cells/μL) 1, 2
• Elevated Aspergillus fumigatus-specific IgE on testing 1
• Elevated Aspergillus fumigatus-specific IgG antibodies 1

Radiologic Red Flags

Chest Radiograph Findings

• Fleeting or transient pulmonary infiltrates that predominate in upper lobes and may be bilateral 1
• "Glove-finger" or band shadows representing mucus-filled bronchi 1
• "Ring sign" or "tram lines" (parallel shadows) indicating inflamed bronchi 1
• Infiltrates that may resolve after coughing up mucus plugs 1

CT Scan Findings

• Central bronchiectasis (pathognomonic when present in asthmatic patients) 1, 2
• High-attenuation mucus plugs on CT imaging 1
• "Tree-in-bud" pattern from mucus plugging 3
• Centrilobular nodules with or without bronchiectasis 1

Algorithmic Approach to Clinical Suspicion

Step 1: Identify the At-Risk Patient

Screen for ABPA if the patient has:

• Asthma (especially corticosteroid-dependent) OR
• Cystic fibrosis OR
• Non-CF bronchiectasis OR
• COPD with recurrent exacerbations 1

Step 2: Recognize Suggestive Clinical Patterns

Suspect ABPA when you observe:

• Poor asthma control despite guideline-based therapy 1
• Recurrent pulmonary infiltrates on serial imaging 1, 2
• Brown or green mucus plugs in sputum 1
• Sustained worsening (≥2 weeks) of respiratory symptoms 1

Step 3: Check Screening Laboratory Tests

Order immediately:

• Total serum IgE (threshold ≥500 IU/mL for diagnosis) 1
• Complete blood count with differential (looking for eosinophilia) 1, 2
• Aspergillus fumigatus-specific IgE (more sensitive than skin testing) 1

Step 4: Obtain Appropriate Imaging

• Chest radiograph to identify fleeting infiltrates or characteristic shadows 1
• High-resolution CT chest to detect bronchiectasis, mucus plugging, or high-attenuation mucus 1

Common Pitfalls and How to Avoid Them

Pitfall 1: Dismissing ABPA in Patients Without Bronchiectasis

• ABPA can present as ABPA-S (serological ABPA) without bronchiectasis 1
• Absence of bronchiectasis does not exclude the diagnosis 1

Pitfall 2: Confusing ABPA Exacerbations with Simple Asthma Exacerbations

• ABPA exacerbations show sustained worsening ≥2 weeks, new infiltrates on imaging, and serum total IgE increase ≥50% above baseline 1
• Asthma exacerbations lack elevated IgE or new infiltrates and respond to short-course glucocorticoids 1
• Bronchiectasis (infective) exacerbations show clinical worsening without IgE elevation ≥50%, with positive sputum bacterial cultures 1

Pitfall 3: Overlooking ABPA in Patients With Atypical Presentations

• ABPA can present as acute respiratory failure requiring ICU admission 4
• Complete bronchial obstruction by sticky material may be the presenting feature 4
• Consider ABPA even in patients without known asthma history if other criteria are met 4

Pitfall 4: Missing the Diagnosis in CF Patients

• CF patients already have bronchiectasis and Aspergillus colonization, making diagnosis challenging 1
• Focus on immunological criteria (elevated IgE, eosinophilia, Aspergillus-specific antibodies) rather than structural changes alone 1

Differential Diagnosis Considerations

When ABPA is suspected, actively exclude:

• Chronic eosinophilic pneumonia (lacks Aspergillus sensitization and elevated IgE) 3, 5
• Churg-Strauss syndrome (systemic vasculitis features, ANCA positivity) 3, 5
• Drug-induced pulmonary infiltrates (temporal relationship with medication) 3
• Parasitic infections (travel history, stool studies) 3, 5
• Nontuberculous mycobacterial infection (positive cultures, different treatment) 3
• Lymphoma (constitutional symptoms, lymphadenopathy) 3

Key Diagnostic Threshold

The European Respiratory Society mandates:

• Demonstration of fungal sensitization (A. fumigatus-specific IgE positive) AND
• Serum total IgE ≥500 IU/mL AND
• Two of the following: fungal-specific IgG, peripheral blood eosinophilia, or suggestive imaging findings 1

This threshold is more sensitive than the older 1000 IU/mL cutoff and should be used in clinical practice 1.