Classification of Interstitial Lung Abnormalities
Interstitial lung abnormalities (ILAs) are classified into three distinct radiologic subtypes based on the 2025 American Thoracic Society guidelines: nonsubpleural, subpleural nonfibrotic, and subpleural fibrotic patterns 1.
The Three ILA Subtypes
1. Nonsubpleural ILA
- Ground-glass opacities or reticular changes that are not predominantly located in the subpleural regions
- Generally carries the lowest risk of progression
- Requires monitoring but typically has better prognosis
2. Subpleural Nonfibrotic ILA
- Interstitial changes located predominantly in the subpleural regions
- Lacks features of fibrosis (no traction bronchiectasis or honeycombing)
- Intermediate risk for progression
- May include ground-glass opacities or mild reticulation in peripheral distribution
3. Subpleural Fibrotic ILA (Highest Risk)
- Most clinically significant subtype with the greatest likelihood of progression and poorest prognosis 2, 3
- Characterized by:
- Traction bronchiectasis (distortion of airways due to fibrotic pull)
- Honeycombing (clustered cystic airspaces)
- Reticulation with architectural distortion
- Predominantly basal and peripheral distribution
- This pattern demands closest surveillance and most aggressive management
Critical Diagnostic Thresholds
ILAs must involve >5% of any lung zone to meet diagnostic criteria 1. This distinguishes ILAs from more extensive interstitial lung disease (ILD), which requires:
- Fibrotic abnormalities involving >5% of total lung volume (not just a single zone)
- OR presence of major fibrotic ILD patterns (UIP/probable UIP, fibrotic hypersensitivity pneumonitis, or fibrotic NSIP)
When ILA Becomes ILD
The 2025 ATS guidelines specify that ILAs transition to clinically significant ILD when any of the following criteria are met 1:
Imaging criteria:
- Fibrotic abnormalities (honeycombing and/or reticulation with traction bronchiectasis) involving >5% of total lung volume
- Progressive fibrotic abnormality on serial chest CT
- Presence of a major fibrotic ILD pattern (UIP/probable UIP, fibrotic HP, or fibrotic NSIP)
Clinical criteria:
- Any dyspnea or cough attributed to ILD
- Abnormal FVC, TLC, or DLCO below lower limit of normal attributed to ILD
- Meets criteria for progressive pulmonary fibrosis
Pathology criteria:
- Histopathologic evidence of major fibrotic ILD pattern
Key Clinical Pitfalls to Avoid
Do not confuse ILA with these mimics 3:
- Dependent atelectasis (changes with patient positioning)
- Centrilobular nodularity (typically infectious or inflammatory)
- Suboptimal inspiration (pseudo-ground-glass appearance)
- Osteophyte-related artifacts
- Apical caps or pleuroparenchymal fibroelastosis-like lesions
- Aspiration or acute infection
Risk Stratification Algorithm
High-risk features requiring closer surveillance 2, 3, 4:
- Subpleural fibrotic pattern (most important)
- Basal and peripheral predominance
- Older age
- Active smoking or significant smoking history
- Genetic risk factors (MUC5B promoter variant)
- Abnormal pulmonary function tests
- History of pneumotoxic medication, radiation, or thoracic surgery
The subpleural fibrotic subtype is associated with increased mortality and higher rates of progression to clinically significant ILD 3, 4, 5, making accurate subtype classification essential for determining appropriate follow-up intervals and intervention timing.