Disease-Specific Guidelines for Listing for Lung Transplantation

Introduction

1. Chronic Obstructive Pulmonary Disease (COPD) / Emphysema

Criteria for Referral:

• BODE index score 5-6 (Body mass index, airflow Obstruction, Dyspnea, Exercise)
• FEV1 <25% predicted
• Resting hypoxemia (PaO2 <60 mmHg) or hypercapnia (PaCO2 >50 mmHg)
• Significant emphysema-related pulmonary hypertension
• Rapid decline in FEV1

Criteria for Listing:

• BODE index score ≥7
• FEV1 <20% predicted with either DLCO <20% or homogeneous distribution of emphysema
• History of acute exacerbation associated with acute hypercapnia (PaCO2 >50 mmHg)
• Pulmonary hypertension or cor pulmonale despite oxygen therapy
• FEV1 <20% with DLCO <20% or homogenous distribution

Key note: The BODE index (score 0-10) predicts 4-year mortality better than FEV1 alone. A score ≥7 is strongly associated with poor prognosis and supports listing.

2. Idiopathic Pulmonary Fibrosis (IPF) / Interstitial Lung Disease (ILD)

Criteria for Referral (any of the following):

• Histopathological or radiographic evidence of UIP (Usual Interstitial Pneumonia) or NSIP pattern
• FVC <80% predicted or DLCO <40% predicted
• Any oxygen requirement (exertional or resting)
• Any significant dyspnea or functional limitation attributable to ILD
• 10% decline in FVC over 6 months or 15% decline in DLCO over 6 months

Criteria for Listing:

• DLCO <39% predicted
• ≥10% decline in FVC during 6 months of follow-up
• Decrease in 6-minute walk distance (6MWD) to <250 m or ≥50 m decline in 6MWD over 6 months
• SpO2 <88% on 6-minute walk test
• Honeycombing on HRCT (fibrosis score >2)
• Pulmonary hypertension on echocardiography or right heart catheterization

Fishman's: "Patients with significant lung function decline, those with oxygen dependency, and those whose posttransplant life expectancy exceeds their current life expectancy without transplant stand to benefit from transplantation." - Fishman's Pulmonary Diseases and Disorders

3. Cystic Fibrosis (CF) and Non-CF Bronchiectasis

Criteria for Referral:

• FEV1 <30% predicted or rapid decline in FEV1 (especially in young female patients)
• 6MWD <400 m
• Development of pulmonary hypertension
• Increasing frequency/severity of exacerbations
• Worsening nutritional status despite supplementation
• Pneumothorax or massive hemoptysis

Criteria for Listing:

• FEV1 <30% predicted (or >30% with rapid decline)
• 6MWD <400 m
• Oxygen-dependent respiratory failure
• Hypercapnia (PaCO2 >50 mmHg)
• Pulmonary hypertension
• Hospitalization for pulmonary exacerbation (especially requiring non-invasive ventilation)
• Life-threatening hemoptysis despite bronchial artery embolization

Special consideration: Multi-drug resistant organisms (e.g., Burkholderia cenocepacia genomovar III) can be a relative or absolute contraindication depending on the centre. Pre-transplant sinus surgery may be considered. Non-CF bronchiectasis uses the same referral and listing criteria as CF.

4. Pulmonary Arterial Hypertension (PAH)

Criteria for Referral:

• ESC/ERS intermediate or high risk OR REVEAL risk score ≥8 despite appropriate PAH therapy
• Significant right ventricular (RV) dysfunction despite appropriate treatment
• Need for IV or subcutaneous (SC) prostacyclin therapy
• Progressive disease despite appropriate combination therapy
• Pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH) - refer at diagnosis
• Secondary liver or kidney dysfunction
• Potentially life-threatening complications (recurrent hemoptysis, large pulmonary artery aneurysms)

Criteria for Listing:

• ESC/ERS high risk OR REVEAL risk score >10 on appropriate therapy, including IV/SC prostacyclin analogues
• Progressive hypoxemia, especially in PVOD or PCH
• Progressive (but not end-stage) liver or kidney dysfunction due to PAH
• Life-threatening hemoptysis

WHO Groups for transplant consideration: Group 1 (PAH) is the primary indication. Group 2 (left heart disease) is NOT an indication. Group 3 (parenchymal lung disease + PH) can be considered. Group 4 (CTEPH) may be treated by pulmonary endarterectomy or balloon pulmonary angioplasty first before considering transplant.

Key tools used: REVEAL 2.2 Registry score and 2015 ESC/ERS risk stratification tools guide listing decisions.

5. Sarcoidosis

Criteria for Referral:

• NYHA/WHO functional class III or IV despite treatment
• Resting hypoxemia
• Pulmonary hypertension
• 6MWD <400 m

Criteria for Listing:

• Any of the above with progressive decline
• Additional consideration for sarcoidosis-related cardiomyopathy or hepatic involvement may require heart-lung or multi-organ transplant evaluation

6. Lymphangioleiomyomatosis (LAM)

Criteria for Referral:

• FEV1 <70% predicted or DLCO <70% predicted
• Exercise limitation or oxygen requirement

Criteria for Listing:

• FEV1 <40% predicted or DLCO <40% predicted
• Hypoxemia at rest (SpO2 <88%)
• Markedly impaired exercise tolerance (6MWD <400 m)

Summary Table: Key Listing Parameters by Disease

General Contraindications (Absolute)

• Malignancy in the last 2 years (exception: some non-melanoma skin cancers)
• Advanced dysfunction of another vital organ (unless combined transplant planned)
• Uncorrectable bleeding diathesis
• Active or recent mycobacterial infection
• Active substance addiction (tobacco, alcohol, illicit drugs)
• Documented non-adherence or inability to comply with the medical regimen
• Psychiatric or psychosocial conditions precluding safe transplantation
• Lack of reliable social support

General Contraindications (Relative)

• Age >65 years
• BMI >35 or <17 kg/m²
• Severe/symptomatic osteoporosis
• Extensive prior thoracic surgery
• Mechanical ventilatory support (though no longer absolute at many centres)
• Highly sensitized patients (PRA >25%)

Key Points for MD Exams

1. BODE index is the key tool for COPD - score ≥7 supports listing, not FEV1 alone.
2. IPF carries the worst prognosis - refer early; any oxygen dependence warrants referral.
3. CF requires bilateral lung transplant; MDR organisms (especially B. cenocepacia III) may be a contraindication.
4. PAH: Group 1 is the main indication; PVOD/PCH should be referred at diagnosis due to limited medical options.
5. The REVEAL 2.2 score and ESC/ERS risk stratification are the two tools used for PAH listing.
6. Non-CF bronchiectasis uses the same criteria as CF.
7. Decline in 6-minute walk distance (6MWD) is a universal marker across diseases.
8. The ISHLT 2021 consensus document (Leard et al.) is the current authoritative reference.