What is the newer classification of Interstitial Lung Disease (ILD)?

Newer Classification of Interstitial Lung Disease

The 2013 ATS/ERS classification represents the current standard framework, organizing ILD into major idiopathic interstitial pneumonias (IIPs), rare IIPs, and unclassifiable IIPs, while introducing critical new behavioral descriptors including Progressive Pulmonary Fibrosis (PPF/PF-ILD) that directly impact treatment decisions. 1, 2

Major Structural Categories

The updated classification divides ILD into four primary categories 3:

• ILDs of known cause: Including drug-induced ILD, collagen vascular disease-associated ILD (representing ~20% of cases), and environmental/occupational exposures such as hypersensitivity pneumonitis 3
• Idiopathic interstitial pneumonias: Seven distinct entities with varying prognoses 1
• Granulomatous lung diseases: Including sarcoidosis and other granulomatous conditions 3
• Unique entities: Miscellaneous conditions not fitting other categories 3, 4

Major Idiopathic Interstitial Pneumonias

The seven major IIPs include 1:

• Idiopathic Pulmonary Fibrosis (IPF): Accounts for 55% of IIPs with 5-year survival worse than many cancers 3
• Idiopathic Nonspecific Interstitial Pneumonia (NSIP): Now accepted as a specific clinicopathologic entity, representing 25% of IIPs with variable prognosis depending on cellular versus fibrotic pattern 1, 3
• Respiratory Bronchiolitis-Interstitial Lung Disease (RB-ILD): Increasingly diagnosed without surgical biopsy in smokers based on clinical/imaging features and bronchoalveolar lavage findings 1
• Desquamative Interstitial Pneumonia (DIP): Smoking-related ILD with better prognosis than IPF 1
• Cryptogenic Organizing Pneumonia (COP): Reversible entity with good response to corticosteroids 1
• Acute Interstitial Pneumonia (AIP): Rapidly progressive with diffuse alveolar damage pattern 1
• Lymphoid Interstitial Pneumonia (LIP): Moved to rare category as most cases are secondary 1

Rare Idiopathic Interstitial Pneumonias

A new category created in 2013 includes 1:

• Idiopathic Lymphoid Interstitial Pneumonia: Moved from major to rare category as most cases are associated with other conditions; few idiopathic cases remain 1
• Idiopathic Pleuroparenchymal Fibroelastosis (PPFE): Upper lobe predominant pleural and subpleural fibrosis with elastosis, presenting at median age 57 years with 60% disease progression and 40% mortality 1, 2

Rare Histologic Patterns (Not Distinct IIPs)

These patterns are recognized but not classified as distinct IIPs 1:

• Acute Fibrinous and Organizing Pneumonia (AFOP): Intraalveolar fibrin deposition without classical hyaline membranes; may be idiopathic or associated with connective tissue disease, hypersensitivity pneumonitis, or drug reaction 1
• Bronchiolocentric patterns: Including peribronchiolar metaplasia-ILD, though data remain insufficient to support these as distinct IIPs 1

Unclassifiable IIP Category

Accounts for approximately 5% of surgical lung biopsies where multidisciplinary discussion cannot achieve >50% diagnostic certainty 2:

• Common causes of unclassifiability: Inadequate clinical/radiologic/pathologic data, major discordance between findings, or previous therapy substantially altering findings 1, 2
• Four-tier diagnostic certainty framework: Standardizes communication about diagnostic confidence and enables more precise prognostic discussions 2

Critical New Behavioral Classification

Progressive Pulmonary Fibrosis (PPF/PF-ILD) represents the most clinically significant addition, defined by three components 2:

• Symptom progression: Worsening dyspnea or cough 2
• Physiologic decline: ≥5% FVC decline over 12 months (associated with ~2-fold mortality increase) 2
• Radiologic progression: Increasing fibrosis on HRCT 2

This phenotype can occur across multiple ILD subtypes including fibrotic hypersensitivity pneumonitis, CTD-related ILD, fibrotic NSIP, and PPFE 2. Antifibrotic therapy (nintedanib or pirfenidone) slows annual FVC decline by approximately 44-57% in PPF regardless of underlying ILD subtype, representing a paradigm shift from restricting antifibrotics to IPF alone 2, 3.

Five Behavioral Patterns for Clinical Management

The ATS/ERS guidelines provide behavioral classification 3:

• Reversible and self-limited: Many RB-ILD cases; requires exposure removal and monitoring 3
• Reversible with risk of progression: Requires close monitoring 3
• Stable with residual disease: Maintenance therapy considerations 3
• Progressive but potentially stabilizable: Aggressive immunosuppression 3
• Progressive despite therapy: IPF pattern; requires antifibrotics and transplant evaluation 3

Rapidly Progressive ILD (RP-ILD)

A distinct descriptive term for patients progressing from wellness to respiratory failure within days to weeks, primarily in MDA-5 positive inflammatory myopathy 2. Do not confuse RP-ILD with PPF/PF-ILD—these represent completely different disease trajectories requiring distinct management approaches 2.

Multidisciplinary Diagnosis Requirement

Accurate classification mandates integration of pulmonology, radiology, and pathology expertise through formal multidisciplinary discussion 1, 3. Approximately half of "unclassifiable" cases can be classified when clinical and radiologic data are properly integrated 2. High-resolution CT has central diagnostic importance with formal UIP pattern criteria, while surgical lung biopsy remains the gold standard when HRCT is non-diagnostic 3.

Key Clinical Pitfalls to Avoid

• Never restrict antifibrotic therapy to IPF alone: The PPF phenotype justifies antifibrotic treatment across multiple ILD subtypes demonstrating progression 2, 3
• Never label cases "unclassifiable" without formal multidisciplinary discussion: This reduces diagnostic accuracy and treatment precision 2
• Never confuse acute exacerbation with primary disease: Acute exacerbation occurs in IPF and other fibrosing IIPs, showing new ground-glass opacities/consolidation superimposed on existing fibrosis; exclude infection and heart failure before diagnosis 1