The Who, What and I have nothing to disclose When

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The Who, What and When: Candidate Selection in Lung

Transplantation

Steven Hays, MDAssociate Professor

Medical Director, Lung TransplantationUCSF Medical Center

Disclosures

I have nothing to disclose

Number of Transplants by Type per Year

NOTE: This figure includes only the lung transplants that

are reported to the ISHLT Transplant Registry. As such, this should not be construed as representing changes in the number of lung transplants performed worldwide.

J Heart Lung Transplant. 2011 Oct; 30 (10) 1071-1132 18181818

Organ Shortage

• 1,923 lung transplants performed in the US last year

• BUT 2,474 candidates added to the wait list

• California alone performed 212 transplants but added 273 patients to the list in 2013

• As of May 1st, 206 patients are waiting for lung transplant in California

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Given the limits of organ availability, it is imperative that teams select patients who are likely to sustain a survival benefit

18181818

Lung TransplantationIndications

• A consensus document for the selection of lung transplant candidates - JHLT January 2015

• Chronic advanced lung disease

• Failed medical management

• Primary goal is improved duration of life but improved quality of life is also a consideration

• For most patients the ultimate “treatment” rather than cure

• Trading one medical condition for another

The Journal of Heart and Lung Transplantation, Vol 34, No 1, January 2015

The Who and What?

• Pulmonary Vascular Disease

• PAH

• PH secondary to systemic disease

• Eisenmenger’s syndrome

• Obstructive Lung Disease

• COPD

• A1ATd

• Suppurative Lung Disease

• Cystic Fibrosis

• Bronchiectasis

• Restrictive Lung Disease

• IPF

• NSIP

• Sarcoidosis

• Eosinophilic granuloma

• LAM

• Occupational lung disease

• Hypersensitivity neumonitis

• Bronchiolitis obliterans

JHLT. 2013 Oct; 32(10): 965-978

Lung TransplantMajor Indications By Year

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UCSF Transplant Recipient CharacteristicsDeceased Donor Transplants Patients transplanted between 01/01/2010 and

12/31/2010

UCSF Region US

PAH 8.7 5.8 5.5

CF 8.7 14.0 14.5

IPF 65.2 47.5 45.8

COPD 17.4 31.9 29.9

Other 0 0.8 4.2

Timing of ReferralGeneral Recommendations

• High risk (>50%) of death due to lung disease within 2 years if lung transplant not performed

• High likelihood (>80%) of surviving at least 90 days after lung transplantation

• High likelihood (>80%) of 5–year post – transplant survival from a general medical perspective provided there is good graft function

• Early referral is highly desirable

• Aids in the psychology of accepting and confronting life-threatening illness

• Aids in actively managing end-stage illness


Absolute Contraindications� Malignancy

• Within 2 years except basal and squamous cell of skin

• 5 years disease free for breast CA > stage 2, colon > Dukes A, melanoma > level III or extra-capsular renal cell CA

• Untreatable advanced organ dysfunction

• Untreatable atherosclerotic disease

• Acute medical instability

• Active TB

• Heart disease

• Cardiomyopathy

• Ungraftable CAD

• Significant chest wall/spinal deformity

• Class II or III obesity (BMI > 35)

• Major psychosocial derangement or Non-adherence

• Current tobacco or drug use


Relative Contraindications

• Age > 65 years if low reserve or other relative contraindications

• Critical or unstable condition

• Severely limited functional status

• Colonization with highly resistant or virulent bacteria

• Class I obesity: BMI 30-35

• Severe malnutrition

• Severe osteoporosis

• Extensive prior chest surgery

• Hepatitis B or C, HIV

• Infections with B. cepacia, B gladioli, M. abscessus


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Recipient Age Distribution by Era

0000

5555

10101010

15151515

20202020

25252525

18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 >65

% o

f Tra

nspl

ants

Recipient Age

1985-1994 (N=4,740)

1995-2004 (N=16,277)

2005-6/2012 (N=22,406)

p < 0.0001Median age by era (years)

1985-1994 = 47

1995-2004 = 51

2005-6/2012 = 55

Adult Lung TransplantsKaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2011)

All pair-wise comparisons were significant at p < 0.05 except 18-34 vs. 35-49

Short and Medium Term Survival Similar in >65 and <65

15Mahidhara R. J Thorac Cardiovasc Surg 2008;135:412-420 Expert Rev Respir Med. 2012 Feb 6(10) 51-61

Factors Potentially Related to Aging and LTx Mortality

� Co-morbidities

� Frailty

� Sarcopenia

� Sarcopenic Obesity

� Co-morbidities

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Body Composition and Survival

� 9073 adults who underwent transplantation in the US between 2005-2011

� Multi-variable regression adjusted models examined the associations between BMI and 1 year mortality

� Underweight (BMI < 18.5) was associated with a 35% increased rate of death

� Class II-III obesity (BMI > 35) was associated with a 2 fold increase in mortality

� Class 1 obesity (BMI 30-34.9) not associated with one year mortality

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Body Composition and Survival

American Journal of Respiratory and Critical Care Medicine 190:9, 971-973

Thabut. J Thorac Cardiovasc Surg 2003;126:469

Pulmonary FibrosisPre-LAS

J Heart Lung Transplant 2006; 25: 745-55

Pulmonary FibrosisDisease Specific Guidelines

If IPF

REFER EARLY

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Referral Guidelines

•UIP

•Fibrotic NSIP

•Oxygen requirement

•FVC < 80% or DLCO < 40%

Listing Guidelines

•10% drop in FVC over 6 months

•15% drop in DLCO over 6 months

•Desaturation with 6MWT or drop in 6MWT distance

•Pulmonary hypertension or hospitalization

Pulmonary FibrosisDisease Specific Guidelines


• Rare, progressive ILD triggered by inhaled antigens

• Primary treatment is removal of antigen from environment

• Offending agent only ID’d in 40% of cases

• A subset of patients develop progressive fibrosis

• Can Lung Transplantation help this group?

• What is the outcome including survival?

• Does it recur?

Hypersensitivity Pneumonitis

• Retrospective cohort study of 31 patients transplanted for HP between 2001-2013

• 12 of 31 had known inciting exposure (39%)

• 5 of the 31 had diagnosis of IPF prior to transplant


Lung Transplantation for Hypersensitivity Pneumonitis. Chest. 2014

• 2 of the 31 patients developed recurrent HP

• Both cases were associated with:

• Exposure to presumed antigen

• Granulomas on biopsy

• Drop in lung function

• No infectious cause

• Improvement/stabilization with treatment with steroids



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Connective Tissue Disease-Related ILD

Adult Lung Transplantation: Indications (1/1995-6/2010)

DIAGNOSIS SLT (N = 12,339) BLT (N = 18,334) TOTAL (N = 30,673)

COPD/Emphysema 5,769 ( 46.8% ) 4,839 ( 26.4% ) 10,608 ( 34.6% )

Idiopathic Pulmonary Fibrosis 3,995 ( 32.4% ) 2,938 ( 16.0% ) 6,933 ( 22.6% )

Cystic Fibrosis 214 ( 1.7% ) 4,941 ( 26.9% ) 5,155 ( 16.8% )

Alpha-1 728 ( 5.9% ) 1,225 ( 6.7% ) 1,953 ( 6.4% )

Idiopathic Pulmonary Arterial Hypertension

78 ( 0.6% ) 894 ( 4.9% ) 972 ( 3.2% )

Pulmonary Fibrosis, Other 424 ( 3.4% ) 537 ( 2.9% ) 961 ( 3.1% )

Bronchiectasis 50 ( 0.4% ) 815 ( 4.4% ) 865 ( 2.8% )

Sarcoidosis 236 ( 1.9% ) 547 ( 3.0% ) 783 ( 2.6% )

Re-Transplant: Obliterative Bronchiolitis 253 ( 2.1% ) 219 ( 1.2% ) 472 ( 1.5% )

Connective Tissue Disease 127 ( 1.0% ) 232 ( 1.3% ) 359 ( 1.2% )

Obliterative Bronchiolitis (Not Re-Transplant)

80 ( 0.6% ) 237 ( 1.3% ) 317 ( 1.0% )

LAM 101 ( 0.8% ) 207 ( 1.1% ) 308 ( 1.0% )

Re-Transplant: Not Obliterative Bronchiolitis

127 ( 1.0% ) 162 ( 0.9% ) 289 ( 0.9% )

Congenital Heart Disease 43 ( 0.3% ) 224 ( 1.2% ) 267 ( 0.9% )

Cancer 6 ( 0.0% ) 26 ( 0.1% ) 32 ( 0.1% )

Other 108 ( 0.9% ) 291 ( 1.6% ) 399 ( 1.3% )

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

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Lung transplantation in scleroderma compared with IPF and IPAH

Arthritis & Rheumatism 2006. pages 3954-3961

Freedom from BOSScleroderma vs. IPF

Transplantation. 2013 Apr 15;95(7):975-80.

Lung Transplant SurvivalScleroderma vs IPF

Transplantation. 2013 Apr 15;95(7):975-80.

Scleroderma and Aspiration Risk

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Scleroderma and Aspiration Risk

34343434

• Severe pulmonary fibrosis (FVC and DLCO <40%), unresponsive to medical treatment

• Creatinine clearance above 60 mL/min

• Absence of severe skin involvement (severe cutaneous thickening)

• Absence of severe esophageal dysmotility and aspiration

• Absence of significant conduction abnormalities

• Absence of severe small intestine, gastroparesis, colorectal and rectum involvement such as pseudo-obstruction, diverticulitis, and perforation

Scleroderma Evaluation

• Retrospective case series of 14 lung transplant recipients with telomerase complex mutations

• All had fibrotic lung disease but only 43% had UIP pattern on CT imaging

• High incidence of cytopenias, particularly leukopenia, post transplantation (83%)

• Of these, 5 could not tolerate anti-proliferative agents – but not associated with acute rejection or CLAD

• CLAD occurred in 33% of recipients at median 3.1 years

Outcomes of Lung Transplantation in Patients with Telomerase Mutations

Outcomes of Lung Transplantation in Patients with Telomerase Mutations

J Heart LungTransplant in press

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IPF Exacerbation

• Acute Deterioration due to right heart strain

• Intubation can make worse

• Traditionally lung transplantation has not been on option for those with respiratory failure

• Reluctance because of concern for dismal outcome

• Allocation of lungs (based on time on wait list)

• Experience with ECLS and MV as well as change in LAS have shifted this paradigm

Nathan SD, Noble PW, and Tuder RM AJRCCM Vol 175. pp. 875-880, (2007)

ECMO as a Bridge to Lung Transplant

UCSF ExperienceECMO Bridge to Transplant

• 31 patients bridged to transplant using ECMO

• 93% survival at 1 year

• 80% survival at 3 years

• 66% survival at 5 years

J Thorac Cardiovasc Surg. 2013 Mar;145(3):862-7

ConsensusECMO Bridge to Transplant

• Recommended

• Young age

• Absence of multiple organ dysfunction

• Good potential for rehabilitation

• Not Recommended

• Septic shock

• Multi-organ dysfunction

• Severe arterial occlusive disease

• HIT

• Prior prolonged mechanical ventilation

• Advanced age and Obesity


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Referral Guidelines

•FEV1 < 30% predicted

•FEV1 > 30% with rapid decline

•6MWD < 400m

•Increasing exacerbations

•ICU admissions

•Recurrent hemoptysis

Listing Guidelines

•PaCO2 > 50 mmHg

•PaO2 < 60 mmHg

•Pulmonary Hypertension

Cystic FibrosisDisease Specific Guidelines

Kerem et al. N Engl J Med 1992; 326: 1187-1191The Journal of Heart and Lung Transplantation, Vol 34, No 1, January 2015

NTM Disease

• All referred for transplant should be evaluated for NTM

• NTM should be ID’d and Tx prior to transplantation

• Progressive disease due to NTM despite Tx or inability to tolerate Tx can be a contraindication

B cepacia complex

• Species other than cenocepacia are not at increased risk

• Cenocepacia results in increased risk of mortality and should be considered with extreme caution

Cystic FibrosisSpecial Considerations


COPDDisease Specific Guidelines

Listing Guidelines

•BODE index of 7-10

•FEV1 < 20% predicted

•Hospitalizations

•Hypercapneicrespiratory failure

•Pulmonary hypertension

•Unacceptable QOL


Pulmonary HypertensionDisease Specific Guidelines

Referral Guidelines

•NYHA III or IV

•Rapidly progressive disease

•Pulmonary venoocclusive disease

Listing Guidelines

•Functional status:

• NYHA III or IV

• Low exercise tolerance (< 350m in 6MW)

• Syncope, hemoptysis or right heart failure

•CI < 2 L/min m2

•RAP > 15 mmHg


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ADULT LUNG TRANSPLANTATIONKaplan-Meier Survival by Era (Transplants: January 1988 – June 2009)

1988-1994: 1/2-life = 4.7 Years; Conditional 1/2-life = 7.9 Years

1995-1999: 1/2-life = 4.8 Years; Conditional 1/2-life = 7.5 Years

2000-6/2009: 1/2-life = 5.9 Years; Conditional 1/2-life = 8.0 Years

N at risk =552

N at risk = 702

N at risk = 841

J Heart Lung Transplant. 2011 Oct; 30 (10) 1071-1132

UCSF, National and Expected Lung Transplant SurvivalData from the Scientific Registry of Transplant Recipients

July 2014

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Thank youQuestions?

Lung Transplant Referrals: (415) 353-4145

Documents

The Who, What and I have nothing to disclose When