What is the appropriate follow-up and management for an adult patient with no significant past medical history and a chest computed tomography (CT) scan showing ground glass opacity with mosaic attenuation?

Follow-Up for Ground Glass Opacity with Mosaic Attenuation on Chest CT

The finding of ground glass opacity (GGO) with mosaic attenuation on chest CT in an adult with no significant past medical history most strongly suggests hypersensitivity pneumonitis (HP), and you should immediately pursue a detailed exposure history (particularly for mold, birds, and occupational antigens), obtain high-resolution CT (HRCT) with expiratory images to assess for air-trapping, and consider bronchoalveolar lavage if the diagnosis remains uncertain. 1

Understanding the CT Pattern

The combination of GGO with mosaic attenuation is highly characteristic of HP and represents a critical diagnostic clue:

• Mosaic attenuation with GGO creates the pathognomonic "three-density sign" (areas of ground-glass opacity adjacent to normal lung adjacent to areas of decreased attenuation), which is highly specific for HP 1
• This pattern reflects the bronchiolocentric distribution of inflammation in HP, where parenchymal infiltration (GGO) occurs adjacent to small airway disease (air-trapping causing decreased attenuation) 1
• The "typical HP" pattern on HRCT requires both parenchymal infiltration findings (GGO or mosaic attenuation) AND small airway disease findings (ill-defined centrilobular nodules or air-trapping) in a diffuse distribution 1

Immediate Diagnostic Steps

1. Obtain Proper HRCT Imaging

• Request dedicated HRCT with both inspiratory AND expiratory images to definitively assess for air-trapping, which is essential for diagnosing HP 1
• Expiratory images will accentuate lobules of decreased attenuation representing air-trapping that may be subtle on inspiratory images alone 1
• Use thin sections (1.5 mm) with multiplanar reconstructions 1

2. Detailed Exposure History

Focus your history on these specific high-yield exposures: 1

• Avian exposure: Pet birds, feather pillows, down comforters, proximity to pigeons
• Mold exposure: Water damage in home/workplace, visible mold, humidifiers, hot tubs
• Occupational exposures: Farming, metalworking fluids, woodworking, textile work
• Timing: Correlation between exposure and symptom onset/worsening

3. Laboratory Testing

• Do NOT rely on serum antigen-specific IgG/IgA antibody testing to confirm or exclude HP - these tests have poor standardization, high false-positive rates (cross-reactivity), and high false-negative rates 1
• Consider basic inflammatory markers and autoimmune serologies to evaluate for alternative diagnoses 2

Differential Diagnosis Considerations

While HP is the leading diagnosis, mosaic attenuation with GGO can also occur in:

Small Airway Disease

• Infectious bronchiolitis, constrictive bronchiolitis 3
• Distinguished by clinical context and absence of typical HP features 3

Vascular Disease

• Pulmonary veno-occlusive disease (PVOD) if centrilobular GGO occurs with septal lines and mediastinal adenopathy (100% specificity for PVOD) 4
• Evaluate for signs of pulmonary hypertension clinically 4

Infiltrative Processes

• Drug-induced pneumonitis (organizing pneumonia pattern, NSIP pattern) - requires recent drug exposure history 5, 4
• Other interstitial pneumonias (NSIP, organizing pneumonia) 5

When to Pursue Invasive Testing

Consider bronchoalveolar lavage (BAL) if: 1, 2

• The diagnosis remains uncertain after HRCT and exposure history
• BAL lymphocytosis >30% suggests HP or other diagnoses (not IPF) 2
• BAL can help differentiate HP from other ILDs when HRCT is not definitive 2

Surgical lung biopsy should be considered if: 2

• HRCT findings are indeterminate and BAL is non-diagnostic
• Multidisciplinary discussion determines biopsy is necessary for definitive diagnosis 2

Management Algorithm Based on CT Pattern

If "Typical Nonfibrotic HP" Pattern (Profuse GGO nodules + mosaic attenuation with three-density sign)

• High confidence for HP diagnosis 1
• Pursue antigen identification and avoidance aggressively 1
• Consider corticosteroids if symptoms are significant 1

If "Compatible with Nonfibrotic HP" Pattern (Patchy GGO + mosaic attenuation, less profuse)

• Moderate confidence for HP 1
• Proceed with BAL if exposure history is unclear 1, 2
• Multidisciplinary discussion recommended 2

If Fibrotic Features Present (Reticulation, traction bronchiectasis, honeycombing)

• This represents fibrotic HP - more challenging to distinguish from IPF 1
• The three-density sign with fibrosis is "typical fibrotic HP" 1
• Requires multidisciplinary discussion with pulmonology, radiology, and pathology 2

Critical Pitfalls to Avoid

• Do not diagnose HP based on serum antibody testing alone - insufficient evidence supports this approach 1
• Do not perform antigen-specific inhalation challenge testing - lacks reliable diagnostic utility and carries risk of adverse effects 1
• Do not assume all GGO with mosaic attenuation is malignant - while solitary GGO lesions can represent early lung cancer, the mosaic attenuation pattern with diffuse distribution strongly favors HP over malignancy 6, 7
• Do not delay obtaining expiratory CT images - air-trapping may only be apparent on expiratory views and is essential for diagnosis 1
• Do not initiate treatment before establishing a specific diagnosis through multidisciplinary discussion 2

Follow-Up Strategy

• If transient inflammatory process suspected (high eosinophil count, recent infection): Short-term follow-up HRCT in 3 months may show resolution 6
• If HP confirmed: Serial HRCT and pulmonary function tests to monitor for progression to fibrosis 2
• If diagnosis remains uncertain: Proceed to BAL and/or multidisciplinary discussion rather than prolonged observation 1, 2