What is the definition of interstitial lung abnormalities?

Definition of Interstitial Lung Abnormalities

Interstitial lung abnormalities (ILAs) are nondependent bilateral parenchymal abnormalities detected on chest CT, including ground-glass or reticular abnormalities, lung distortion, traction bronchiectasis, and/or honeycombing involving ≤5% of a lung zone by visual estimate, but without meeting criteria for interstitial lung disease. 1

Core Diagnostic Criteria

The 2025 American Thoracic Society clinical statement provides the most current and authoritative definition, building upon the Fleischner Society Position Paper with updated evidence:

Required CT Features (All Must Be Present):

• Bilateral involvement (with rare exceptions in high-risk populations)
• Nondependent location - abnormalities must persist on prone imaging if initially seen in dependent areas on supine scans
• Limited extent - ≤5% of any single lung zone affected
• Does not meet ILD criteria - this is the critical distinguishing feature

Specific Parenchymal Patterns Include:

• Ground-glass opacities
• Reticular abnormalities
• Lung architectural distortion
• Traction bronchiectasis
• Honeycombing

The lung is divided into six zones (upper, middle, lower on each side) demarcated by the inferior aortic arch and right inferior pulmonary vein levels. 1

Three ILA Subtypes with Different Prognostic Implications

The classification system has direct clinical relevance for risk stratification:

1. Nonsubpleural ILA

• Patchy ground-glass and peribronchovascular opacities
• Minimal reticular changes
• Often upper lung zone predominance
• Lowest risk for progression 1

2. Subpleural Nonfibrotic ILA

• Bilateral subpleural reticulations
• No traction bronchiectasis or honeycombing
• Intermediate risk profile 1

3. Subpleural Fibrotic ILA

• Bilateral subpleural reticulations with traction bronchiectasis
• May include honeycombing
• Architectural distortion defines fibrosis
• Highest risk for progression to ILD and poorest prognosis 1, 2

Critical Distinctions from ILD

ILAs become reclassified as ILD when any of the following occur:

Imaging Criteria:

• Fibrotic abnormalities (honeycombing and/or reticulation with traction bronchiectasis) involving >5% of total lung volume (note: total volume, not per zone)
• Progressive fibrotic abnormality on serial CT
• Presence of major fibrotic ILD pattern (UIP/probable UIP, fibrotic hypersensitivity pneumonitis, or fibrotic NSIP) 1

Clinical/Physiological Criteria:

• Respiratory symptoms attributable to ILD
• Abnormal pulmonary function testing
• Pathology showing major fibrotic ILD pattern 1

The threshold shifts from ≤5% per lung zone (for ILA definition) to >5% total lung volume (for ILD definition) to capture more diffuse involvement and enhance specificity. 1

Important Caveats and Pitfalls

When Unilateral Findings May Still Be Relevant:

Despite the bilateral requirement, unilateral abnormalities warrant attention in:

• Patients with strong family history of familial pulmonary fibrosis
• Known ILD-associated genetic variants (e.g., MUC5B promoter variant)
• Connective tissue disease
• Occupational exposures

However, progression risk data for unilateral cases remains limited, and findings often represent non-ILA etiologies. 1

Features That Don't Count Toward the 5% Threshold:

• Nonemphysematous cysts
• Centrilobular nodularity
• Features of pleuroparenchymal fibroelastosis

These can be present but don't contribute to volume calculations. 1

Avoiding False Positives:

Confirm that abnormalities are truly nondependent - mild changes exclusively in dependent locations on supine imaging must persist on prone imaging to qualify as ILA. This prevents overcalling physiologic atelectasis as pathology. 1

Evolution of the Definition

The 2025 ATS statement deliberately removed two previous requirements:

1. No longer requires findings to be "incidental" - ILAs can be identified in any clinical context
2. No longer excludes high-risk populations - ILAs can occur in smokers, those with occupational exposures, etc., as these populations may still have non-progressive abnormalities from postinfectious or aspiration-related causes 1

This makes the definition more practical for radiologists who often lack complete clinical context and acknowledges that even high-risk individuals can have stable, non-progressive findings.

Clinical Significance

ILAs represent a spectrum from inconsequential radiological findings to early ILD. Prevalence ranges from 2.5-16.7% in screening populations, with higher rates in older individuals and smokers. 3 Progression to ILD occurs in 20-80% depending on subtype and risk factors. 4, 3 The subpleural fibrotic subtype carries the greatest likelihood of progression and is associated with increased mortality. 2, 5