What are the characteristic high-resolution computed tomography (HRCT) thoracic imaging findings in hypersensitivity pneumonitis?

HRCT Thorax Findings in Hypersensitivity Pneumonitis

The characteristic HRCT findings in hypersensitivity pneumonitis depend on whether the disease is nonfibrotic or fibrotic, with the key diagnostic requirement being the presence of BOTH parenchymal infiltration AND small airway disease features together. 1, 2

Nonfibrotic HP: Classic HRCT Features

Parenchymal Infiltration Patterns

• Ground-glass opacities (GGO) appear as diffusely distributed areas of increased attenuation that do not obscure underlying vessels 1, 2
• Mosaic attenuation manifests as a patchwork pattern of varying lung densities on inspiratory images, created by GGO adjacent to normal-appearing lung 1, 3
• The distribution is typically diffuse in both craniocaudal and axial planes, sometimes with relative basal sparing 1, 2

Small Airway Disease Features (Essential for Diagnosis)

• Ill-defined centrilobular nodules measuring less than 5 mm appear on inspiratory images 1, 2
• Air trapping becomes evident on expiratory CT images, showing lobular areas of decreased attenuation 1, 2
• These small airway features are mandatory - their absence makes the HRCT indeterminate for HP regardless of other findings 2

Critical Diagnostic Point

The 2020 ATS/JRS/ALAT guidelines emphasize that typical nonfibrotic HP requires at least one parenchymal infiltration finding PLUS at least one small airway disease finding, both in diffuse distribution 1. This combination is what distinguishes HP from other interstitial lung diseases 4, 5.

Fibrotic HP: Advanced Disease Features

Fibrosis Patterns

• Irregular fine or coarse reticulation with architectural lung distortion is the hallmark finding 1, 2
• Traction bronchiectasis appears in areas of GGO, indicating fibrotic change 1, 2
• Septal thickening may be present, often associated with the reticulation 1, 2
• Honeycombing can occur but is typically minimal; extensive honeycombing suggests severe disease 1

The "Three-Density Pattern" (Pathognomonic Finding)

• This highly specific sign shows three distinct lung densities sharply demarcated from each other on the same image 1, 2, 3:
  • High attenuation areas (GGO from active inflammation)
  • Lucent lung (air trapping from small airway disease)
  • Normal-appearing lung parenchyma
• The ATS/JRS/ALAT guidelines note this pattern is pathognomonic for fibrotic HP and helps differentiate it from idiopathic pulmonary fibrosis 1, 2
• Five or more lobules of mosaic attenuation in each of three or more lobes bilaterally has high specificity for fibrotic HP 3

Distribution Patterns in Fibrotic HP

• Fibrosis is most severe in mid or mid-lower lung zones, with characteristic relative basal sparing 1, 2
• On axial images, there is often no central or peripheral predominance 1
• This distribution pattern is crucial for distinguishing fibrotic HP from usual interstitial pneumonia (UIP), which shows basal and peripheral predominance 6

Essential Caveat for Fibrotic HP

Coexisting lung fibrosis and signs of bronchiolar obstruction together are required for the diagnosis 1, 2. The presence of a UIP pattern alone without small airway disease features is indeterminate for HP and cannot establish the diagnosis 2.

Optimal HRCT Acquisition Protocol

Technical Parameters (Per ATS/JRS/ALAT Guidelines)

• Noncontrast examination with volumetric acquisition 1
• Submillimetric collimation with shortest rotation time and highest pitch 1
• Thin-section images less than 1.5 mm thickness, contiguous or overlapping 1
• High-spatial-frequency reconstruction algorithm (iterative reconstruction if validated) 1

Critical Acquisition Requirements

• Both inspiratory AND expiratory acquisitions are mandatory 1, 2:
  • Inspiratory: volumetric acquisition at full inspiration
  • Expiratory: sequential or volumetric to evaluate air trapping
• Prone positioning is optional but can help differentiate dependent attenuation from true disease 1
• Recommended radiation dose: 1-3 mSv (reduced dose protocol) 1, 2
• The guidelines strongly recommend avoiding ultra-low-dose CT (less than 1 mSv) as it may miss critical findings 1

Common Pitfalls and How to Avoid Them

Pitfall #1: Missing Small Airway Disease

The most critical error is diagnosing HP based on fibrosis patterns alone without identifying small airway disease features 2. Always obtain expiratory images to evaluate for air trapping, as this may be the only clue to small airway involvement 1, 2.

Pitfall #2: Confusing Mosaic Attenuation with Other Patterns

Mosaic attenuation in HP shows the characteristic three-density pattern, whereas vascular causes (like chronic thromboembolic disease) show different vessel caliber in affected areas 3. The presence of centrilobular nodules alongside mosaic attenuation strongly favors HP 1, 5.

Pitfall #3: Misdiagnosing Chronic HP as UIP/IPF

Chronic fibrotic HP can mimic usual interstitial pneumonia 6. Key distinguishing features favoring HP include:

• Mid-lung or upper-lung predominance rather than basal predominance 1, 2
• Presence of the three-density pattern 1, 2
• Relative basal sparing 1, 2
• Any evidence of small airway disease (centrilobular nodules, air trapping) 2

Pitfall #4: Inadequate Technical Protocol

Using only inspiratory images or ultra-low-dose protocols will miss air trapping and subtle centrilobular nodules 1, 2. The 2020 guidelines provide specific technical parameters that should be followed 1.

Integration with Clinical Context

HRCT findings alone are insufficient for definitive diagnosis 2, 3. The imaging must be integrated with:

• Detailed exposure history (birds, mold, hot tubs, agricultural exposures) 7
• Clinical presentation and pulmonary function tests 7
• Bronchoalveolar lavage findings (lymphocytosis greater than 20% with CD4/CD8 ratio less than 1 supports HP) 7
• Multidisciplinary discussion is recommended for definitive diagnosis, especially when HRCT patterns are indeterminate 2, 3

Recent evidence from 2025 confirms that the amount of HP-compatible features on HRCT has excellent predictive ability (AUC 0.85), with air trapping being the strongest independent predictor 8. However, the positive predictive value remains modest, reinforcing the need for clinical-radiologic integration 8.