What are the indications and contraindications for lung transplant in patients with Interstitial Lung Disease (ILD)?

Indications and Contraindications for Lung Transplantation in Interstitial Lung Disease

For patients with interstitial lung disease (ILD), early referral for lung transplantation evaluation is strongly recommended when there is evidence of disease progression despite optimal medical management, as this intervention provides significant survival benefit in appropriate candidates. 1

Indications for Lung Transplantation in ILD

Primary Indications

• Progressive physiologic deterioration despite optimal medical therapy 1
• Oxygen dependency 1
• Deteriorating clinical course 1
• Specific pulmonary function criteria:
  • FVC < 80% predicted 2
  • DLCO < 40% predicted 2
  • Need for high-flow oxygen (marker of severity warranting transfer to transplant center) 1

Disease-Specific Considerations

• Rapidly Progressive ILD (RP-ILD): Early referral for lung transplantation is conditionally recommended over later referral after progression on optimal medical management 1
• Systemic Autoimmune Rheumatic Disease (SARD)-associated ILD: Early referral is conditionally recommended when presenting with advanced disease 1
• Idiopathic Pulmonary Fibrosis (IPF): Currently the most common indication for lung transplantation worldwide 3

Contraindications for Lung Transplantation

Absolute Contraindications

• Unstable or inadequate psychosocial profile/stability 1
• Significant extrapulmonary disorders that may negatively influence survival:
  • Liver dysfunction 1
  • Renal dysfunction 1
  • Cardiac dysfunction 1

Relative Contraindications

• Advanced age (many centers limit candidates to those < 60 years) 1
• Inability to tolerate the procedure (particularly relevant in RP-ILD patients being considered for stem cell transplantation) 1

Timing of Referral

Early Referral Rationale

• Limited donor availability (waiting time may exceed 2 years) 1
• Pre-transplantation evaluation requires significant time 1
• Options for medical therapy may be influenced by transplant candidacy 1
• Early referral allows for better preparation and planning 1

Current Referral Patterns

• Significant under-referral exists (only 30.7% of eligible ILD patients are referred for transplant evaluation) 2
• Median time from meeting PFT criteria to referral: 255 days 2
• Median time from referral to transplantation: 89 days 2

Outcomes After Lung Transplantation

Survival Benefits

• 5-year survival rates after transplantation: 50-60% 1, 4
• Median survival after transplantation: 5.2-6.7 years (compared to <2 years in advanced ILD without transplant) 4
• Single-lung transplantation is currently the preferred surgical approach for most ILD patients 1

Post-Transplant Improvements

• Improved arterial oxygen tension (often eliminating need for supplemental oxygen) 1
• Increased lung volumes and DLCO 1
• Reversal of pulmonary hypertension and right ventricular dysfunction 1
• Improved quality of life 4

Complications

• Graft failure, infection, and heart failure (early mortality) 1
• Bronchiolitis obliterans, infection, and malignancy (late mortality) 1
• Patients transplanted during acute exacerbations of ILD can have acceptable outcomes with careful selection 5

Special Considerations

Systemic Sclerosis-Associated ILD

• Mycophenolic acid is the preferred initial treatment before considering transplantation 6
• Consider adding nintedanib if there is progression of ILD 6
• Avoid long-term corticosteroids 6

Acute Exacerbations

• Patients with acute exacerbations can be transplanted with acceptable 1-year outcomes (93% survival) with careful selection 5
• In rare circumstances, mechanical ventilation may be appropriate as a bridge to lung transplantation 1

Clinical Approach to Lung Transplant Referral in ILD

1. Monitor pulmonary function with respiratory function tests every 3-6 months 6
2. Refer early when any of the following are present:
   • FVC < 80% predicted or DLCO < 40% predicted 2
   • Oxygen dependency 1
   • Progressive decline despite optimal medical therapy 1
3. Conduct pre-transplant evaluation including:
   • Assessment for extrapulmonary organ dysfunction 1
   • Psychosocial evaluation 1
   • Screening for pulmonary hypertension 6
4. Maintain optimal medical management while awaiting transplantation 1

Common Pitfalls in Lung Transplant Referral for ILD

• Delayed referral: Associated with increased morbidity and mortality 2
• Age bias: Older patients are less likely to be referred despite meeting criteria 2
• Overreliance on "better" PFT values: Patients with relatively better PFTs are often not referred despite meeting criteria 2
• Failure to recognize disease progression: Regular monitoring is essential to identify candidates early 6
• Waiting until respiratory failure: By this point, patients may be too ill for successful transplantation 1

Early referral to a transplantation center is warranted even if not local for the patient, as patients and families are generally agreeable to traveling away from home for potentially life-saving measures 1.