What is interstitial lung disease (ILD)?

Interstitial Lung Disease (ILD)

Interstitial lung disease (ILD) is a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the lung parenchyma, affecting the interstitium, alveolar spaces, small airways, vessels, and sometimes the pleura, leading to progressive respiratory impairment and potential respiratory failure.

Definition and Epidemiology

ILD encompasses a diverse collection of more than 200 pulmonary disorders that diffusely affect the lung parenchyma with variable patterns of inflammation and fibrosis. Key characteristics include:

• Affects approximately 650,000 people in the US with 25,000-30,000 deaths annually 1
• Prevalence estimates range from 25-74 per 100,000 population 2
• Higher incidence in men (31.5 per 100,000) than women (26.1 per 100,000) 2
• Accounts for approximately 15% of patients seen by pulmonologists 2

Classification

ILDs are typically classified into three main categories:

1. Known causes or associations:

   • Connective tissue disease-associated ILD (CTD-ILD) - accounts for 25% of ILD cases 1
   • Occupational/environmental exposures
   • Drug-induced ILD

2. Idiopathic interstitial pneumonias (IIP):

   • Idiopathic pulmonary fibrosis (IPF) - accounts for approximately one-third of all ILD cases 1
   • Nonspecific interstitial pneumonia (NSIP)
   • Desquamative interstitial pneumonia (DIP)
   • Respiratory bronchiolitis with interstitial lung disease (RBILD)
   • Acute interstitial pneumonia (AIP)
   • Cryptogenic organizing pneumonia (COP)
   • Lymphoid interstitial pneumonia (LIP)

3. Granulomatous disorders:

   • Sarcoidosis
   • Hypersensitivity pneumonitis (HP) - accounts for 15% of ILD cases 1

Clinical Presentation

Common symptoms and signs include:

• Dyspnea on exertion - primary presenting symptom 1
• Chronic dry cough - occurs in approximately 30% of patients 1
• Bibasilar inspiratory crackles on chest examination
• Progressive respiratory impairment
• Potential development of pulmonary hypertension (up to 85% in end-stage fibrotic ILD) 1

Diagnostic Approach

Diagnosis requires a multidisciplinary approach:

1. High-Resolution CT (HRCT):

   • Gold standard for confirming ILD diagnosis
   • 91% sensitive and 71% specific for diagnosing ILD subtypes 1
   • Pattern recognition is crucial (UIP, NSIP, HP patterns) 3

2. Pulmonary Function Tests (PFTs):

   • Typically show restrictive pattern (reduced FVC, normal FEV1/FVC ratio)
   • Reduced diffusion capacity (DLCO)
   • Baseline FVC and DLCO are important prognostic indicators 3

3. Bronchoalveolar Lavage (BAL):

   • Useful for specific ILD patterns 2
   • BAL cell differential counts with:

     • 15% lymphocytes: lymphocytic pattern

     • 3% neutrophils: neutrophilic pattern

     • 1% eosinophils: eosinophilic pattern

     • 0.5% mast cells: mastocytosis 2

4. Lung Biopsy:

   • Surgical lung biopsy or transbronchial lung cryobiopsy
   • Recommended for patients with indeterminate HRCT patterns 3

Treatment Approaches

Treatment must be tailored to the specific ILD subtype:

1. Idiopathic Pulmonary Fibrosis (IPF)

• Antifibrotic therapy:
  • Nintedanib or pirfenidone are first-line treatments 3, 1
  • Both slow annual FVC decline by approximately 44-57% 1
  • Pirfenidone reduced mean decline in FVC by 193 mL compared to placebo in clinical trials 4

2. Connective Tissue Disease-Associated ILD (CTD-ILD)

• Immunomodulatory therapy:
  • Mycophenolate mofetil is the preferred first-line agent for most CTD-ILDs 3
  • Short-term corticosteroids may be considered (except in systemic sclerosis) 3
  • For systemic sclerosis-ILD (SSc-ILD), nintedanib is conditionally recommended as first-line 3
  • Tocilizumab is a conditionally recommended alternative for SSc-ILD 3

3. Progressive Fibrosing ILD

• For ILD with progression, options include:
  • Mycophenolate
  • Rituximab
  • Cyclophosphamide
  • Nintedanib 3

4. Supportive Care

• Oxygen therapy for patients who desaturate below 88% on exertion 1
• Pulmonary rehabilitation and structured exercise therapy 1
• Vaccination (influenza, pneumococcus, COVID-19) 3
• Pneumocystis jirovecii pneumonia prophylaxis for patients on high-dose corticosteroids 3

5. Advanced Disease Management

• Lung transplantation should be considered for patients with advanced ILD 3, 1
• Median survival after lung transplant is 5.2-6.7 years compared to less than 2 years without transplant for advanced ILD 1

Monitoring and Prognosis

• Regular monitoring with PFTs every 3-6 months for moderate-to-severe ILD 3
• A 5% decline in FVC over 12 months is associated with doubled mortality 3, 1
• Disease progression is defined as:
  • Decline in FVC ≥10% predicted
  • Decline in FVC 5-10% with worsening symptoms or increased fibrosis on HRCT
  • Worsening symptoms with increased fibrosis 3

Important Considerations

• Early diagnosis is crucial for optimal management but often delayed due to nonspecific symptoms
• Multidisciplinary discussion involving pulmonologists, radiologists, and pathologists is the gold standard for diagnosis
• Progressive phenotypes require more aggressive therapy and closer monitoring
• Comorbidities such as pulmonary hypertension may require specific management