What is unclassified interstitial lung disease (ILD)?

From the Guidelines

Unclassified interstitial lung disease (ILD) is a diagnosis given when a patient has clinical, radiological, and sometimes histological evidence of interstitial lung disease, but the findings don't fit into any of the well-defined ILD categories despite thorough evaluation, occurring in approximately 10-25% of all ILD cases. This diagnosis represents a complex and heterogeneous group of diseases that do not meet the specific criteria for other ILD categories, such as idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, or connective tissue disease-associated ILD 1. The inability to accurately classify cases is usually the result of several factors, including the lack of a biopsy, discrepant or overlapping histopathological findings, discrepant features between clinical, radiological, and pathological findings, or significant overlapping clinical or radiological features that preclude diagnosis 1.

Key Characteristics

• Represents approximately 10-25% of all ILD cases
• Occurs when the disease pattern shows overlapping features or atypical characteristics that prevent classification into specific entities
• Diagnosis is made after thorough evaluation, including clinical, radiological, and sometimes histological evidence
• Management involves monitoring disease progression with pulmonary function tests and high-resolution CT scans every 3-6 months, with treatment decisions made on a case-by-case basis 1

Management

• Monitoring disease progression with pulmonary function tests and high-resolution CT scans every 3-6 months
• Treatment decisions made on a case-by-case basis, with consideration of anti-inflammatory medications, immunosuppressants, or antifibrotic medications
• Some patients may receive anti-inflammatory medications like prednisone or immunosuppressants such as mycophenolate mofetil or azathioprine, particularly if inflammation predominates
• Antifibrotic medications like pirfenidone or nintedanib might be considered in cases with progressive fibrosis 1

Diagnostic Framework

• A proposed framework for diagnosing interstitial lung disease involves dividing patients into four tiers following multidisciplinary discussion (MDD): those with confident diagnosis, provisional diagnosis with high confidence or low confidence, and unclassifiable interstitial lung disease 1
• The goal of this framework is to help standardize the terminology of fibrotic lung disease and decrease the number of patients categorized as having unclassifiable interstitial lung disease 1

From the Research

Definition and Characteristics of Unclassified Interstitial Lung Disease

• Unclassified interstitial lung disease (ILD) comprises a subset of ILDs that cannot be classified according to the current diagnostic framework 2, 3.
• This condition is likely a heterogeneous group of diseases rather than a single entity, and it is poorly defined, making prognosis and therapy problematic 2.
• Approximately 12% of patients with ILD are considered unclassifiable, with large variability across previous studies due to inconsistent definitions of unclassifiable ILD and other ILD subtypes 3.

Diagnosis and Management

• Accurate diagnosis of ILD can be challenging, and a substantial percentage of ILD patients remain unclassifiable even after thorough assessment by an experienced multidisciplinary team 3, 4.
• Clinical features and outcomes of unclassifiable ILD are intermediate between idiopathic pulmonary fibrosis and nonidiopathic pulmonary fibrosis ILD cohorts, and choices for pharmacotherapy should be considered on a case-by-case basis 3.
• New tools are needed to more accurately characterize patients with unclassifiable ILD 3.

Prevalence and Impact

• Interstitial lung disease (ILD) consists of a group of pulmonary disorders characterized by inflammation and/or fibrosis of the lung parenchyma associated with progressive dyspnea that frequently results in end-stage respiratory failure 5.
• In the US, ILD affects approximately 650 000 people and causes approximately 25 000 to 30 000 deaths per year 5.
• Up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis 4.