Is lung transplantation indicated for patients with interstitial lung disease, and what are the eligibility criteria?

Lung Transplantation in Interstitial Lung Disease

Yes, lung transplantation is a critical therapeutic option for patients with advanced or progressive ILD who meet eligibility criteria, and early referral is strongly recommended to optimize outcomes. 1, 2

Indications for Lung Transplantation in ILD

Lung transplantation should be considered for patients with ILD who meet the International Society for Heart and Lung Transplantation (ISHLT) criteria, particularly those with: 1, 3

• Age <65 years with severe functional impairment 3
• DLCO <39% predicted 3
• FVC decline ≥10% over 6 months 3, 4
• Severe hypoxemia requiring high-flow oxygen 1, 2
• 6-minute walk distance <250 meters 4
• Progressive physiologic deterioration despite optimal medical management 3, 2

The most common ILD subtypes undergoing transplantation include idiopathic pulmonary fibrosis (IPF), which now represents the leading indication for lung transplantation worldwide, followed by fibrotic hypersensitivity pneumonitis, sarcoidosis, and connective tissue disease-associated ILD. 5, 6

Timing of Referral: Early is Critical

For patients with systemic autoimmune rheumatic disease-associated ILD (SARD-ILD), early referral for lung transplantation evaluation is conditionally recommended over waiting for further progression on optimal medical management. 1 This recommendation is particularly important because:

• Pre-transplantation evaluation takes considerable time 1, 2
• The need for high-flow oxygen is a marker of severity warranting immediate transfer to a transplant center 1
• Patients with rapidly progressive ILD (RP-ILD) should receive immediate referral for transplant evaluation 2, 7
• A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality, making early identification crucial 6

For patients with IPF and related fibrotic ILDs, early referral is especially critical due to the risk of acute exacerbation and accelerated development of respiratory failure. 8

Eligibility Criteria and Contraindications

Relative contraindications to lung transplantation include: 3

• Age >60-65 years 3
• Unstable or inadequate psychosocial profile/stability 3
• Significant extrapulmonary disorders 3

Surgical Approach

Single lung transplantation is currently the preferred surgical procedure for fibrotic ILD, including IPF and asbestosis, according to established guidelines. 3, 9 This preference is based on:

• Organ scarcity considerations, as bilateral transplantation uses organs that could benefit two patients 3
• Similar survival outcomes compared to bilateral transplantation in non-suppurative ILD 9

However, bilateral lung transplantation is reserved for patients with suppurative lung disease or significant pulmonary hypertension. 9

Expected Outcomes

Post-transplant outcomes in ILD patients include: 3, 6

• Arterial oxygen tension sufficiently improved to eliminate supplemental oxygen requirement 3
• Lung volumes and DLCO increased 3
• Pulmonary hypertension and right ventricular dysfunction reversed 3
• 5-year survival approximates 50-60% after transplantation 3
• Median survival of 5.2-6.7 years post-transplant compared to less than 2 years in advanced ILD patients who do not undergo transplant 6

Disease-Specific Considerations

Pulmonary Alveolar Proteinosis (PAP)

Lung transplantation is conditionally recommended for patients with PAP progressing despite whole lung lavage and/or pharmacological treatment who fulfill ISHLT criteria for ILD. 1 Available data from case reports demonstrate that lung transplantation reversed chronic hypoxic respiratory failure in the majority of reported cases. 1

Systemic Sclerosis-Associated ILD (SSc-ILD)

For SSc-ILD patients with progression despite first-line treatment, referral to a lung transplantation center is recommended rather than waiting for further progression. 2 Additionally, stem cell transplantation at specialized centers with proven expertise should be considered for appropriate candidates. 2

Critical Pitfalls to Avoid

• Do not delay pulmonology referral until symptoms become severe 2
• Do not wait for disease progression before considering lung transplantation referral in appropriate candidates 2
• Do not manage ILD in isolation—co-management by rheumatologists and pulmonologists is essential for optimal outcomes 1, 2
• Do not underestimate the time required for pre-transplant evaluation; early referral allows adequate time for assessment and listing 1, 2

Pre-Transplant Management

While awaiting transplantation, patients should receive: 3

• Long-term oxygen therapy for severe hypoxemia at rest 3
• Respiratory rehabilitation programs including exercise training, smoking cessation, and psychosocial support 3
• Annual influenza vaccination and anti-pneumococcal vaccination 3
• Monitoring of oxygen saturation at rest and with exertion at 3-6 month intervals 3