What are the management guidelines for interstitial lung diseases (ILDs) according to the 2025 classification, including bronchiolocentric interstitial pneumonia and diffuse alveolar damage?

Management of Interstitial Lung Diseases According to the Latest Classification

Management of interstitial lung diseases (ILDs) should be based on disease behavior classification rather than rigid histopathological patterns, with treatment strategies tailored to the specific ILD subtype including bronchiolocentric interstitial pneumonia and diffuse alveolar damage. 1, 2

Diagnostic Approach for ILD Classification

• High-Resolution CT (HRCT): Gold standard for initial diagnosis with ~91% sensitivity and 71% specificity 2
• Pulmonary Function Tests: Essential for baseline assessment and monitoring progression 2
• Tissue Diagnosis: When needed for classification
  • Transbronchial Lung Cryobiopsy (TBLC): Suggested as first-line approach for histopathological data in patients eligible or ineligible for surgical lung biopsy 1
  • Surgical Lung Biopsy (SLB): Suggested as add-on test if TBLC is non-informative 1

Management Based on Disease Behavior Classification

The American Thoracic Society/European Respiratory Society recommends classifying ILDs based on disease behavior rather than rigid histopathological patterns 1:

1. Reversible and self-limited disease (e.g., many RB-ILD cases)

   • Treatment: Remove causative agent (e.g., smoking cessation for RB-ILD) 1, 3
   • Monitoring: Short-term observation (3-6 months) to confirm regression 1

2. Reversible disease with risk of progression (e.g., cellular NSIP, some fibrotic NSIP, DIP, COP)

   • Treatment: Initial therapy to achieve response, then rationalize long-term treatment 1
   • Monitoring: Short-term observation to confirm treatment response, long-term observation to ensure maintained improvement 1

3. Stable with residual disease (e.g., some fibrotic NSIP)

   • Treatment: Maintenance therapy 1
   • Monitoring: Long-term observation to assess disease course 1

4. Progressive, irreversible disease with potential for stabilization (e.g., some fibrotic NSIP)

   • Treatment: Stabilization therapies 1
   • Monitoring: Long-term observation to assess disease course 1

5. Progressive, irreversible disease despite therapy (e.g., IPF, some fibrotic NSIP)

   • Treatment: Therapies to slow progression 1
   • Monitoring: Long-term observation to assess disease course and need for transplant or palliation 1

Specific Management for Newly Recognized ILD Subtypes

Bronchiolocentric Interstitial Pneumonia

• Recently described entity with bronchiolocentric fibroinflammatory changes 1
• Diagnostic features: Peribronchiolar metaplasia, bronchiolocentric fibrosis 1
• Differential diagnosis: Consider hypersensitivity pneumonitis, occupational exposures, small airway disease 1
• Management:
  • Identify and remove potential causative agents (environmental/occupational exposures) 1
  • Consider treatment similar to hypersensitivity pneumonitis if exposure history present 1
  • Monitor with HRCT and PFTs every 3-6 months 2

Diffuse Alveolar Damage (DAD)

• Common pathological finding in rapidly progressive ILDs 4, 5
• Clinical presentation: Acute respiratory failure, dyspnea, hypoxia 1, 5
• HRCT findings: Bilateral ground-glass opacities, consolidation 5
• Management:
  • High-dose corticosteroids (methylprednisolone 1-2 mg/kg/day) 1
  • Consider immunosuppressants for refractory cases 1, 2
  • Supportive care including oxygen therapy for hypoxemia 2
  • Early referral for lung transplantation in progressive cases 2

Treatment Options Based on ILD Etiology

Connective Tissue Disease-Associated ILD (CTD-ILD)

• First-line treatment: Glucocorticoids combined with immunosuppressive agents (except in systemic sclerosis) 2
• For SSc-ILD:
  • Mycophenolate mofetil (recommended first-line) 2, 6
  • Nintedanib (conditionally recommended) 2, 6
  • Tocilizumab (conditionally recommended) 2
  • Combination therapy may be considered 6

Immunotherapy-Related ILD (IR-ILD)

• Grading: Based on symptom severity and radiological findings 1
• Management: Depends on grade of pneumonitis 1
  • Grade 1 (asymptomatic): Consider holding immunotherapy, monitor closely
  • Grade 2-4: Corticosteroids with dose based on severity, consider permanent discontinuation of immunotherapy in severe cases

Monitoring and Follow-up

• Short-term monitoring: PFTs within 3 months and HRCT within 6 months to determine progression rate 2
• Regular monitoring:
  • Moderate-to-severe ILD: PFTs every 3-6 months
  • Mild ILD (FVC ≥70% and <20% fibrosis on HRCT): PFTs every 6 months 2
• Definition of progression:
  • Decline in FVC ≥10% predicted
  • Decline in FVC 5-10% with worsening symptoms or increased fibrosis on HRCT
  • Worsening symptoms with increased fibrosis 2

Supportive Care

• Oxygen therapy: For patients with resting oxygen levels ≤7.3 kPa or ≤8 kPa with peripheral edema or pulmonary hypertension 2
• Cough management: Gabapentin and speech pathology therapy for refractory cough; low-dose opiates in palliative settings 2
• Preventive care:
  • Pneumocystis jirovecii pneumonia prophylaxis for patients on high-dose corticosteroids 2
  • Calcium and vitamin D supplementation 2
  • Vaccinations (influenza, pneumococcus, COVID-19) 2

Unclassifiable ILD

When ILD cannot be classified despite thorough evaluation:

• Base management on most probable diagnosis after multidisciplinary discussion 1
• Consider disease behavior pattern to guide treatment approach 1
• Consider additional biopsies if initial samples are non-diagnostic 1