RECIPIENT AGE AND LUNG TRANSPLANT Kevin Conroy ST

RECIPIENT AGE AND LUNG TRANSPLANT Kevin Conroy ST 4 Matt Dickson ST 3

Introduction ■ Criteria for lung transplantation ■ Assessment process ■ Ethical considerations ■ Arguments for age limitation ■ Arguments against age limitation

ISHLT Guidance for Lung Transplant Should be considered for patients with chronic, end-stage lung disease who meet following general criteria: 1. High (>50%) risk of death from lung disease within 2 years if lung transplantation is not performed. 2. High (>80%) likelihood of surviving at least 90 days after lung transplantation. 3. High (>80%) likelihood of 5 -year post-transplant survival from a general medical perspective provided that there is adequate graft function.

Absolute: ■ ■ ■ Contraindications Recent history of malignancy Untreatable significant dysfunction of other major organ Uncorrected/untreatable atherosclerotic disease with end-organ ischaemia/dysfunction Acute medical instability Uncorrected hypocoagulopathy Chronic infection with highly virulent/pan-resistant organisms Significant chest wall/spinal deformity BMI >35 Poor compliance to medical therapy Untreated psychiatric/psychological conditions Absence of adequate/reliable social support system Substance abuse or dependence

Contraindications Relative: ■ Age >65 years for single lung transplant, >60 for bilateral ■ BMI <18 or >30 ■ Severely deconditioned with poor rehab potential ■ Colonisation with certain pathogens ■ HIV, Hepatitis B and C ■ Severe, symptomatic osteoporosis ■ Extensive prior chest surgery/lung resection ■ Mechanical ventilation and/or extracorporeal life support ■ Significant atherosclerotic disease

Assessment Process Height, weight and BMI >17, <30 Bloods – FBC, Creatinine clearance, LFT, tissue typing and antibody screen Virology – HIV, Hep B, Hep C, CMV Sputum MCS Urine MSU

Assessment Imaging ■ ■ ■ ■ CXR Latest Images DEXA Perfusion (Q) scan Echocardiogram ECG Angiogram / CT angiogram Ultrasound abdomen/ liver

Assessment ■ PFTS - spirometry, TLC, DLCO ■ 6 MWT – assess exercise capacity ■ Social work / family support

Common issues ■ Lack of recent imaging ■ Deconditioning ■ BMI outside tolerance ■ Outstanding coronary artery assessment

Ethical considerations in organ transplants Medical ethics: Beneficence, non-maleficence, autonomy and justice Distributive justice: ■ Only becomes an issue when scarce resources ■ Thinks about group ethic rather than patient-centred ethic ■ Equal access – Distribution free of bias ■ Maximum benefit – Maximise successful transplants

Controversy surrounding Age Criteria § § § <60 for bilateral lung transplant <65 for single lung transplant Age has been revisited periodically Contradictory evidence Increased complication rates and decreased survival rates among older vs possibility of benefiting younger persons with better outcomes § Other studies show equivocal outcomes § Chronological age vs. Physiological age

Arguments for Age Criteria

ISHLT Registry Report 2015 International heart and lung transplant registry collecting data since 1983 Tracks morbidity and mortality post-transplant ISHLT registry report 2015 summarised data from 51, 440 adult lung transplants 242 Lung transplant centres and 174 Heart-Lung transplant centres provided Report encompassed data up to June 30 th 2014

Findings of the 2015 report ■ 45, 542 adults underwent primary lung transplantation between 1990 and June 2013 ■ Median survival of 5. 7 years ■ Survival rates of 89% at 3 months, 80% at 1 year, 65% at 3 years, 54% at 5 years and 31% at 10 years ■ Those surviving at 1 year had median survival of 7. 9 years ■ Better survival in bilateral lung transplants (7. 1 years vs 4. 5 for single) ■ Better survival in latest era (i. e. between 2009 -2013) ■ Survival also varied for different indications, sex as well as age The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Lung and Heart-Lung Transplantation Report--2015; Focus Theme: Early Graft Failure. Yusen RD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Goldfarb SB, Levvey BJ, Lund LH, Meiser B, Rossano JW, Stehlik J. J Heart Lung Transplant. 2015; 34(10): 1264

Arguments for current age criteria ■ Multiple risk factors for death identified in 17, 755 adult transplants between 2001 -2013 ■ Highest hazard ratios were transplant centre volume and recipient age ■ Increased risk of 1 year post-transplant death began at ~55 years ■ Rises exponentially thereafter

Hazard ratio for mortality within the first post-transplant year for adult lung transplant recipient age and center volume (transplants: January 2001–June 2013). The dashed lines represent 95% confidence intervals.

ISHLT Registry Report 2013 – focus theme: age ■ 66% of recipients for lung transplant were between ages of 45 -65 ■ Since 1985, median age of recipient increased from 45 to 55 ■ 2006 -2012, 10% aged >65, 3% >70 compared with 3% and 0. 3% respectively between 2000 -20052 ■ Mortality rates differed depending on era (most recent, better survival) ■ Increased age of recipient mainly in ILD and COPD (excluding A 1 ATD) ■ Older sub-groups generally had lower long-term survival and Yusen RD, Christie JD, Edwards LB, et al. for the International Society of Heart and Lung Transplantation. Registry of the International Society for Heart and Lung Transplantation: 30 th adult lung younger and heart-lung transplant report– 2013; higher long-term complication rates than sub-groups focus theme: age. J Heart Lung Transplant 2013; 32: 965 -78

ISHLT Registry Report 2013 – focus theme: age ■ Mortality also dependent on indication for transplant: – 3 month mortality rates highest in IPAH (22%), lowest in non-A 1 ATD COPD (9%) – Median survival for those surviving to 1 year highest for CF (10. 5), IPAH (10) and lowest for ILD (7. 0) and non-A 1 ATD COPD (6. 9) ■ Median survival for transplants between 1990 and 2011: – >65 years - 3. 6 years – 60 -65 years - 4. 5 years – 50 -59 years - 5. 3 years – 35 -49 years - 6. 7 years – 18 -34 years - 6. 5 years

ISHLT Registry Report 2013 – focus theme: age ■ Five year survival rates: – >65 years – 38% – 60 -65 years – 46% – 50 -59 years – 52% – 35 -49 years – 57% – 18 -34 years – 55% ■ Interaction between age and indication for transplant – Older recipients within each diagnostic group had worse survival – Non-A 1 ATD COPD had better overall survival compared to ILD – 18 -49: 6. 4 years vs 5. 7 years – 50 -65: 5. 4 years vs 4. 3 years – >65: 3. 7 vs 3. 8 years

Why does increased age lead to poorer outcomes? ■ Chronic kidney disease ■ Diabetes ■ Cardiovascular complications ■ Thromboembolic disease ■ Malignancy

Arguments against Age Criteria

Age isn’t a barrier ■ Distributive justice of finite resource ■ Aging population ■ Shrinking health budget § Improving health in older age § Delaying pension / working longer § Feasibility and better outcomes

Age isn’t a barrier ■ ISHLT guidance suggests ‘physiological’ age of <65 single lung, <60 double lung tx. ■ No absolute age limit ■ ISHLT registry – cumulative – doesn’t reflect newer data ■ Personalized care

Age isn’t an Barrier ■ Delayed pension ■ Societal roles ■ Increased expectation ■ Equality ■ The aim of transplant

Age isn’t a barrier Mahidhara, Bastani et al 2008 ■ No significant difference in survival at 3 years <65 vs >65 ■ Reduced (p=0. 16) survival 1 -12 month period – infection ■ Immunosenescence of age – tx not tailored to older age ■ Freedom from BOS lower at 12/12 but not significant overall But >65 1. 76% SLTx 2. Basiliximab induction c. f ATG 3. Non standardized donor organs Mahidhara et al. Lung transplantation in older patients? Journal of thoracic and cardiovascular surgery 2008

Age isn’t a barrier ■ 182 - 52 >60 years old ■ No significant difference in survival over 5 years (p=0. 61) ■ Mortality slightly worse before 30 days for >60 – probability curves taken from beyond 30 days. ■ In hospital mortality 12% c. f 7% in under 60. ■ All over 65 had SLT Smith et al. Lung transplantation in over 60 years and older: results, complications and outcomes. Journal of the society of thoracic surgeons. 2006

Age isn’t a barrier ■ 2 year period 268 lung tx, 47% aged over 60 ■ No significant difference in survival at 1, 12 and 36 months <60, 60 -65, >65. ■ Similar rates of significant bacterial infecgtion ■ Malignancy and drug toxicity more likely in >65 (p=0. 004), (0. 03) than 60 -65 ■ Rejection more common 60 -65 group c. f >65 Vadnerkar et al Age-specific complications among lung transplant recipients 60 years and older. JHLT 2011

Age isn’t a barrier ■ Improving experience ■ Aging population ■ Social responsibility ■ Acceptable outcomes in transplant Careful patient selection

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