7.1.1 Ethical Principles for the Allocation of Donor Lungs

• Utility: To maximise net benefit (e.g., using years of survival gained to prioritise allocation)

• Justice: To distribute the benefits and burdens of organ allocation system in a fair way (e.g., using medical urgency to prioritise allocation, allowing special consideration for candidates for whom it is difficult to find a suitable organ)

• Respect for persons: To treat persons as autonomous with the right for self-determination (e.g., the right to give or withhold informed consent for lung transplantation).

7.2.1 Inclusion criteria

Indications for lung transplantation are:

• Progressive respiratory failure despite optimal medical, interventional and surgical treatment, and/or

• Poor quality of life, potentially with intractable symptoms and repeated hospital admissions (e.g. New York Heart Association [NYHA] Class III-IV).

Additional disease-specific candidate selection criteria at time of listing

Chronic obstructive pulmonary disease:

• Forced expiratory volume in one second (FEV 1 ) <25 % predicted

• Body-mass, airflow obstruction, dyspnea and exercise (BODE) index ≥7

• Clinical deterioration: severe exacerbation with hypercapnoic respiratory failure or recurrent exacerbations despite maximal treatment, pulmonary rehabilitation, and oxygen therapy

• Moderate to severe pulmonary hypertension

• Chronic hypercapnia.

Cystic Fibrosis:

• FEV 1 <30% predicted especially if a rapid downward trajectory is observed (<40% predicted in children)

• Frequent hospitalisation, (>28 days/year) despite optimal medical therapy i.e., trial of elexacaftor/ tezacaftor/ivacaftor

• Massive haemoptysis (>240ml) despite bronchial artery embolization

• Pneumothorax

• Exacerbations requiring non-invasive ventilation and/or intravenous antibiotics

• 6-minute walk test <400m

• Worsening nutritional status despite nutritional interventions (BMI <18kg/m²)

• Development of pulmonary hypertension (PASP >50mmHg or RV dysfunction)

• PCO 2 >50 mmHg and/or PO 2 <60 mmHg.

Interstitial Lung Disease (ILD):

• Any form of pulmonary fibrosis with forced vital capacity (FVC) of <80% predicted or diffusing capacity of the lungs for carbon monoxide (DLCO) <40% predicted

• Decline in FVC of >10% or decline in DLCO > 10% within the prior 6 months

• Supplementary oxygen requirement at rest and/or exertion

• Development of pulmonary hypertension demonstrated by echo or right-heart catheter

• Hospitalisation because of respiratory decline, acute exacerbation, or pneumothorax

• Desaturation to < 88% on 6 minute walk test or >50 m decline in 6 minute walk test distance in the past 6 months

• Inflammatory ILD – progressive decline of pulmonary function with radiographic progression despite treatment For patients with connective tissue disease or familial pulmonary fibrosis, early referral is recommended as extrapulmonary manifestations may require special consideration.

Pulmonary vascular diseases:

• NYHA Functional class III or IV/REVEAL risk score >10 despite escalation of pulmonary vasodilator therapy

• Progressive hypoxemia

• Significant right ventricle dysfunction despite pulmonary hypertension (PAH) therapy

• Secondary organ decline due to PAH i.e., kidney, liver.

• Known or suspected high-risk variants such as Pulmonary veno-occlusive disease/Pulmonary capilliary hemangiomatosis (PVOD/PCH), scleroderma or large pulmonary artery aneurysms

• Life-threatening complications such as: hemoptysis.

• Lymphangioleiomyomatosis (LAM)

• FEV1 <30% predicted + diseases progression despite mTOR inhibitor therapy

• NYHA Class III or IV

• Hypoxemia at rest

• Pulmonary Hypertension

• Refractory Pneumothorax.

7.2.2 Exclusion criteria

Absolute contraindications to lung transplantation include any condition or combination of conditions that result in an unacceptably high risk of mortality or morbidity, limiting the likely survival benefit from transplantation or the predicted gain in quality of life. Absolute contraindications include (but are not limited to):^2-82 Chambers DC, Perch M, Zuckermann A, et al. International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult lung transplantation report - 2021; Focus on recipient characteristics. J Heart Lung Transplant. 2021 Oct;40(10):1060-1072.3 Leard LE, Holm AM, Valapour M, et al. Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2021 Nov;40(11):1349-1379.4 Barbour KA, Blumenthal JA and Palmer SM. Psychosocial issues in the assessment and management of patients undergoing lung transplantation. Chest, 2006; 129(5): 1367–74.5 Dew AM, DiMartini AF, Dobbels F et al. The 2018 ISHLT/APM/AST/ICCAC/STSW recommendations for the psychosocial evaluation of adult cardiothoracic transplant candidates and candidates for long-term mechanical circulatory support, The Journal of Heart and Lung Transplantation, 2018; 31 (7): 803-823.6 Denhaerynck K, Desmyttere A, Dobbels F, et al. Nonadherence with immunosuppressive drugs: U.S. compared with European kidney transplant recipients. Prog Transplant, 2006; 16(3): 206–14.7 Dobbels F, Verleden G, Dupont L, et al. To transplant or not? The importance of psychosocial and behavioural factors before lung transplantation. Chron Respir Dis, 2006; 3(1): 39–47.8 Hayanga AJ, Aboagye JK, Hayanga HE, et al. Contemporary analysis of early outcomes after lung transplantation in the elderly using a national registry. J Heart Lung Transplant 2015;34:182-8.×

Lack of patient willingness or acceptance of transplant

Malignancy with high risk of recurrence or death related to cancer

Glomerular filtration rate < 40 mL/min/1.73m² unless being considered for multi-organ transplant

Acute coronary syndrome or myocardial infarction within 30 days (excluding demand ischemia)

Stroke within 30 days

Liver cirrhosis with portal hypertension or synthetic dysfunction unless being considered for multi-organ transplant

Acute liver failure

Acute renal failure with rising creatinine or on dialysis and low likelihood of recovery

Septic shock

Active extrapulmonary or disseminated infection

Active tuberculosis infection

HIV infection with detectable viral load

Limited functional status (e.g., non-ambulatory) with poor potential for post-transplant rehabilitation

Progressive cognitive impairment

Repeated episodes of non-adherence without evidence of improvement (Note: For pediatric patients this is not an absolute contraindication and ongoing assessment of non-adherence should occur)

Active substance use or dependence including current tobacco use, vaping, marijuana smoking, or illicit drug use

Other severe uncontrolled medical condition expected to limit survival after transplant

Non-compliance with pre-transplantation vaccinations as recommended by the local transplant unit - the seroconversion rate after vaccinations is significantly higher in the non-immunosuppressed population compared to vaccination in immunosuppressed solid organ transplant recipients^9,109 Yanis A, Haddadin Z, Spieker AJ, et al. Humoral and cellular immune responses to the SARS-CoV-2 BNT162b2 vaccine among a cohort of solid organ transplant recipients and healthy controls. Transpl Infect Dis. 2022 Feb;24(1):e1377210 Schramm R, Costard-Jäckle A, Rivinius R, et al. Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients. Clin Res Cardiol. 2021 Aug;110(8):1142-1149.×

Risk factors with high or substantially increased risk of adverse patient outcome post lung transplantation.

Candidates with these risk factors may be considered in some transplant units with specific expertise³, it is likely that the presence of multiple comorbidities alongside low physiologic reserve in patients over 70 years of age will exclude many of such patients from consideration for lung transplantation.3 Leard LE, Holm AM, Valapour M, et al. Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2021 Nov;40(11):1349-1379.×

Age > 70 years

Severe coronary artery disease that requires coronary artery bypass grafting at time of transplant

Reduced left ventricular ejection fraction < 40%

Significant cerebrovascular disease

Severe esophageal dysmotility

Untreatable hematologic disorders including bleeding diathesis, thrombophilia or severe bone marrow dysfunction

BMI > 35 kg/m²

BMI < 16 kg/m²

Limited functional status with potential for post-transplant rehabilitation

Psychiatric, psychological or cognitive conditions with potential to interfere with medical adherence without sufficient support systems

Unreliable support system or caregiving plan

Lack of understanding of disease and / or transplant despite teaching

Mycobacterium abscessus infection

Lomentospora prolificans infection

Burkholderia cenocepacia or gladioli infection

Hepatitis B or C infection with detectable viral load and liver fibrosis

Chest wall or spinal deformity expected to cause restriction after transplant

Extracorporeal life support

Retransplant <1 year following initial lung transplant

Retransplant for restrictive chronic lung allograft dysfunction (CLAD)

Retransplant for AMR as etiology for CLAD

7.2.3 Retransplantation

Retransplantation may be an appropriate consideration in select candidates should an individual deteriorate after receiving a lung transplant and re-qualifies for waitlisting according to the inclusion and exclusion criteria stated above. Evaluation of retransplantation should explore possible reasons for graft failure, rate of deterioration, donor lung availability and the management of patient’s sensitisation/potential high panel-reactive antibody.

7.3.1 Urgent patients

Although there is no defined national priority/urgent lung listing category, under some circumstances a lung transplant waitlisted patient from one state may be notified to other state Lung Transplant Programmes in an attempt to increase their opportunities for lung allocation and transplantation. This process is termed National Notification. Urgent patients are incorporated into the lung matching algorithm described in Section 7.5.2 and are offered deceased donor lungs as per the ADTCA-TSANZ-OTA National Standard Operating Procedure: Organ Allocation, Organ Rotation, Urgent Listing, also described in Appendix F.

7.3.2 Paediatric patients

The nationally funded centre for paediatric lung transplantation resides at the Alfred Hospital in Melbourne, Victoria, with a recommended age range for referral from four to sixteen years.

7.3.3 Histocompatibility Assessment

Each recipient must undergo a series of tests performed at the state Tissue Typing laboratories. These include:

1. HLA Typing using molecular technique such as Next Generation Sequencing (NGS) at the following HLA loci: A, B, C, DRB1, DQB1, DQA1, DPB1, DPA1,

2. HLA antibody screening using Luminex single antigen beads. This screening must have occurred within 120 days to be included in matching. It is optimal that all waitlisted patients are screened every 3 months.

These tests will be used in the histocompatibility assessment by the Tissue Typing labs and in consultation with the clinical unit to assign Unacceptable Antigens. These assigned unacceptable antigens can assist in excluding a waitlisted patient from incompatible donor offers.

7.4.1 Donor-related risk

Table 7.1 outlines standard criteria for lung donation. Historically, approximately 35-40% of deceased donor lungs offered for donation in Australia and New Zealand have been considered acceptable for clinical transplantation.¹¹ This compares with international retrieval rates of only 15-20%.^12,13,14 Specific management protocols have evolved for the potential lung donor that address common scenarios such as retained secretions, aspiration, ventilator-associated pneumonia, barotrauma prevention, atelectasis and neurogenic pulmonary oedema. A higher- risk lung donor is one who has characteristics that may adversely influence the early and/or long-term transplant outcomes of the chosen recipient. Traditionally, a higher-risk donor has been defined as possessing one of the following characteristics: age >60 years, smoking history >20 pack years, PaO2 <300 mmHg, chest x-ray positive for infiltrates or trauma, persistent purulent secretions at bronchoscopy or prolonged ischaemic time. Nonetheless, many potential donors with these characteristics will prove suitable for lung donation following careful organ assessment and retrieval.^15-23 The evolution of ex-vivo lung perfusion (EVLP) will further enhance acceptance rates for lung donation especially those donors considered very high risk or with multiple risk factors. The EVLP system consists of a perfusion circuit with tubing and a reservoir, enabling lungs to be sustained ex-vivo at normal temperature with an extracellular perfusate rich in human albumin to maintain high colloid pressure. The principles of EVLP are to reduce interstitial oedema within the donated lung and to perform maneuvers to facilitate alveolar recruitment, whilst monitoring the trajectory of key physiological measures including PO2, pulmonary vascular resistance and lung compliance.11 ANZOD Registry. 2022 Annual Report, Section 8: Deceased Donor Lung Donation. Australia and New Zealand Dialysis and Transplant Registry, Adelaide, Australia. 2022. Available at: www.anzdata.org.au ×12 Reyes KG, Mason DP, Thuita L, et al. Guidelines for donor lung selection: time for revision? Ann Thorac Surg, 2010;89(6):1756-64. 13 Botha P, Trivedi D, Weir CJ, et al. Extended donor criteria in lung transplantation: impact on organ allocation. J Thorac Cardiovasc Surg, 2006;131(5):1154-60. 14 Van der Mark SC, Rogier A.S. Hoek, Merel E. Hellemons Developments in lung transplantation over the past decade. European Respiratory Review Sep 2020, 29 (157) 190132; ×15 Bittle GJ, Sanchez PG, Kon ZN, et al. The use of lung donors older than 55 years: a review of the United Network of Organ Sharing database. J Heart Lung Transplant, 2013; 32 (8): 760-768. 16 Schiavon M, Falcoz PE, Santelmo N, et al. Does the use of extended criteria donors influence early and long term results of lung transplantation? Interact Cardiovasc Thorac Surg, 2012; 14 (2): 183-7. 17 Zych B, Garcia-Saez D, Sabashnikov A, et al. Lung transplantation from donors outside standard acceptability criteria – are they really marginal? Transpl Int, 2014; 27 (11): 1183-91. 18 Copeland H, Hayanga JWA, Neyrinck A, MacDonald P, et al. Donor heart and lung procurement: A consensus statement. J Heart Lung Transplant. 2020 Jun;39(6):501-517. 19 Kotecha S, Hobson J, Fuller J, et al. Continued Successful Evolution of Extended Criteria Donor Lungs for Transplantation. Ann Thorac Surg. 2017 Nov;104(5):1702-1709. 20 Botha P, Rostron AJ, Fisher AJ, et al. Current strategies in donor selection and management. Semin Thorac Cardiovasc Surg, 2008; 20(2): 143–51. 21 Snell GI, Westall GP, Oto T. Donor risk prediction: how ‘extended’ is safe? Curr Opin Organ Transplant. 2013 Oct;18(5):507-12. 22 Orens JB, Boehler A, de Perrot M, et al. A review of lung transplant donor acceptability criteria. J Heart Lung Transplant, 2003; 22(11): 1183–200. 23 Snell GI, Westall GP. Selection and management of the lung donor. Clin Chest Med. 2011 Jun;32(2):223-32. ×

Table 7.1: Suitability criteria for lung donation^23,2423 Snell GI, Westall GP. Selection and management of the lung donor. Clin Chest Med. 2011 Jun;32(2):223-32. 24 Van Raemdonck D, Neyrinck A, Verleden GM, et al. Lung donor selection and management. Proc Am Thorac Soc, 2009; 6(1): 28–38. ×

7.4.2 Donor information and testing

Table 7.2: Donor information required for lung allocation

* See Appendix E. Ante mortem interventions such as lung bronchoscopy and CT Chest are commonly deployed in all jurisdictions with minor variations between states and, in some jurisdictions, between hospitals.

7.5.1 General allocation principles

The lung transplant unit in the home state receives the donor offer as detailed below and given 30 minutes to respond to the offer. If the home state lung transplant unit declines the offer, the donation offer is made on rotation to non-home state lung transplant units - with a 30-minute response time, as per the ADTCA-TSANZ-OTA National Standard Operating Procedure - Organ Allocation, Organ Rotation, Urgent Listing.

The acceptance of lungs by a transplant unit depends on a large variety of technical and logistic factors, including the existence of a suitable recipient (see Table 7.3). Although it is known that a variety of factors may manifest as apparent donor lung ‘quality’ (and be measured as oxygenation, chest X-ray abnormalities and bronchoscopy findings), no specific higher-risk donor category is used when allocating lungs or making acceptance decisions.

7.5.2 Lung Matching Algorithm

Considerable logistical issues and the various combinations of potential lung and/or heart transplantation that heart and lung transplant units must consider when donor organs are offered add complexity to the development of a lung matching algorithm.^{25 - 27}25 Snell GI, Esmore DS, Westall GP, et al. The Alfred Hospital lung transplant experience. Clin Transpl 2007: 131–44. 26 Snell GI, Griffiths A, Macfarlane L, et al. Maximizing thoracic organ transplant opportunities: the importance of efficient coordination. J Heart Lung Transplant, 2000; 19(4): 401–07. 27 Orens JB and Garrity ER, Jr. General overview of lung transplantation and review of organ allocation. Proc Am Thorac Soc, 2009; 6(1): 13–19. ×

The OrganMatch Lung TWL matching algorithm uses blood group compatibility, size matching and immunological compatibility to generate a list of potential recipients. The tissue typing laboratory will perform virtual crossmatches (VXM) on the recipients on the waitlist. Patients with unacceptable antigens to the donor HLA typing will be excluded from the match. Whilst OrganMatch enhances the process of recipient matching, the final allocation decision is always at the discretion of the accepting lung transplant unit. Further information on OrganMatch and the lung matching algorithm can be found here: https://www.donatelife.gov.au/for-healthcare-workers/organmatch/ training-hub#Transplantation_Portal

For allocation of lungs from paediatric donors, please refer to Section 11.4.

Table 7.3: Individual patient allocation criteria for donor lungs

Notes:

*Clinical urgency: Graded by level of support required and evidence of rapidity of deterioration of underlying indication for transplant. Level of support includes, but not limited to the following:
— Extracorporeal membrane oxygenator (ECMO)
— Invasive mechanical ventilation
— Non-invasive ventilation
— High-flow O 2 requirement
— Low-flow O 2 requirement
— Prolonged or recurrent hospitalisation
— Other support devices such as continuous intravenous therapies.

Rapidity of deterioration includes, but not limited to
— Change in NYHA functional Class or Medical Research Council(MRC) grade
— Significant fall in lung function parameters
— Significant fall in PaO2
— Significant rise in partial pressure of carbon dioxide in the blood (PaCO2)
— Significant fall in 6-minute walk test distance
— Need for escalation in level of support as above
— Time course of progression of radiological changes
— Development of symptomatic pulmonary hypertension
— Development of refractory right heart failure.

** Logistical considerations include: operation type (lobar, single, bilateral, heart/lung); availability of required team members for the retrieval, lung transplant(s) and related cardiac transplants (paired donor heart or domino heart transplant); timely availability of all recipients; coordination between all involved transplant units arranging and performing the transplant procedures.

***Consideration of long-term outcome benefit includes: Comorbidities such as osteoporosis, gastroesophageal reflux, known coronary or peripheral vascular disease, carriage of pan-resistant organisms, poor rehabilitation potential, history of malignancy, advanced age, lack of compliance, morbid obesity or malnutrition and other relative contraindications for lung transplantation which have been shown to be associated with an inferior outcome benefit.