What is the newer classification of Interstitial Lung Disease (ILD) and how does it impact management and treatment?

Newer Classification of Interstitial Lung Disease

Primary Classification Framework

The 2013 ATS/ERS classification divides ILD into three main categories: Major Idiopathic Interstitial Pneumonias (IIPs), Rare IIPs, and Unclassifiable IIPs, with the critical addition of behavioral descriptors—most importantly Progressive Pulmonary Fibrosis (PPF/PF-ILD)—that now drive treatment decisions independent of the underlying histologic pattern. 1, 2, 3

Major Idiopathic Interstitial Pneumonias

The classification recognizes six major IIPs that account for the vast majority of cases 1:

• Idiopathic Pulmonary Fibrosis (IPF) - represents 55% of all IIPs, carries the worst prognosis with 5-year survival worse than many cancers 1, 2, 4
• Idiopathic Nonspecific Interstitial Pneumonia (NSIP) - now accepted as a distinct clinicopathologic entity (25% of IIPs), with prognosis varying based on cellular versus fibrotic pattern 1, 4
• Respiratory Bronchiolitis-Interstitial Lung Disease (RB-ILD) - increasingly diagnosed without surgical biopsy in smokers based on HRCT showing ground-glass opacities and centrilobular nodules plus BAL showing smoker's macrophages 1
• Desquamative Interstitial Pneumonia (DIP) - smoking-related ILD with better prognosis than IPF 1
• Cryptogenic Organizing Pneumonia (COP) - typically responsive to corticosteroids 1
• Acute Interstitial Pneumonia (AIP) - rapidly progressive with high mortality 1

Rare Idiopathic Interstitial Pneumonias

The updated classification formally recognizes two rare IIPs 1:

• Idiopathic Lymphoid Interstitial Pneumonia (LIP) - accounts for <1% of IIPs 1
• Idiopathic Pleuroparenchymal Fibroelastosis (PPFE) - newly elevated to formal rare IIP category, characterized by upper lobe predominant pleural and subpleural fibrosis with elastosis, presenting at median age 57 years with 60% disease progression and 40% mortality 1, 2, 3

Unclassifiable Idiopathic Interstitial Pneumonias

Unclassifiable ILD accounts for approximately 5% of surgical lung biopsies and occurs in three specific scenarios 1, 3:

• Inadequate clinical, radiologic, or pathologic data 1, 3
• Major discordance between clinical, radiologic, and pathologic findings 1, 3
• Previous therapy substantially altering radiologic or histologic findings (e.g., steroid therapy converting DIP appearance to residual NSIP pattern) 1

Approximately half of "unclassifiable" cases can be reclassified when clinical and radiologic data are properly integrated through multidisciplinary discussion, making formal MDD mandatory before applying this label 2, 3.

Critical Behavioral Classification: Progressive Pulmonary Fibrosis

The most clinically impactful addition to ILD classification is the PPF/PF-ILD phenotype, which describes disease behavior rather than histologic pattern and directly determines antifibrotic therapy eligibility. 2, 3

Definition of PPF/PF-ILD

PPF is defined by three components occurring over 12 months 3:

• Symptom progression (worsening dyspnea or cough) 3
• Physiologic decline (≥5% FVC decline, which is associated with ~2-fold mortality increase) 3
• Radiologic progression (increased fibrosis on HRCT) 3

Treatment Implications

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, 5. This applies across multiple ILD subtypes including fibrotic hypersensitivity pneumonitis, CTD-related ILD, and fibrotic NSIP 3.

Multidisciplinary Diagnosis Requirement

Accurate ILD classification mandates formal multidisciplinary discussion integrating pulmonology, radiology, and pathology expertise, as this dynamic process significantly improves diagnostic accuracy compared to individual specialty assessment 1, 4, 6, 7.

The multidisciplinary approach defines when lung biopsy is informative versus when HRCT alone suffices 1. Academic physicians in multidisciplinary settings demonstrate better diagnostic agreement than community physicians, who are more likely to over-diagnose IPF 1.

Key Diagnostic Integration Points

• Clinical features (age, smoking history, exposures, comorbidities, lung function, laboratory findings) must be integrated with radiologic patterns 1
• Once a pathologic pattern is identified (e.g., NSIP or organizing pneumonia), clinicians must reconsider potential secondary causes including hypersensitivity pneumonitis, collagen vascular disease, and drug exposure 1
• HRCT features suggesting hypersensitivity pneumonitis include centrilobular nodules, mosaic air-trapping, and upper lobe distribution, requiring detailed exposure history even though 30% have no identifiable exposure 1

Common 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, as this reduces diagnostic accuracy and treatment precision 2, 3.

Do not confuse Rapidly Progressive ILD (RP-ILD) with PPF/PF-ILD—RP-ILD describes progression from wellness to respiratory failure within days to weeks (primarily in MDA-5 positive inflammatory myopathy), requiring completely different management with tacrolimus and IVIG rather than antifibrotics 3.

Recognize that smoking-related ILD (RB-ILD, DIP) and combined pulmonary fibrosis and emphysema represent distinct entities that can now be diagnosed without surgical biopsy when clinical, HRCT, and BAL findings are concordant 1.