PowerPoint Presentation · 9/20/2018 1 Lung Diseases and Criteria Leading to Transplant Roger F. Johnson, MD, FCCP Pulmonary and Critical Care Medicine St. Vincent Evansville Medical

9/20/2018

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Lung Diseases and Criteria Leading to Transplant

Roger F. Johnson, MD, FCCP

Pulmonary and Critical Care Medicine

St. Vincent Evansville Medical Center

Evansville, Indiana

Disclosures

• I have no conflicts of interest related to this topic• While I often refer patients for lung transplant and

manage advanced lung disease, I do not practice lung transplant medicine

• I have received honoraria from the following companies:– Bayer (Pulmonary hypertension)– Gilead (Pulmonary hypertension)– Genentech (Idiopathic pulmonary fibrosis)– AstraZeneca (COPD)– Pinnacle Biologics (Photodynamic therapy for lung

cancer)

Objectives

• Understand general criteria for patient selection for lung transplantation

• Discuss absolute and relative contraindications for lung transplantation

• Understand how previous surgery and treatment for pneumothorax affects a patient’s candidacy for lung transplantation

• Understand disease-specific indications for lung transplantation

• Discuss the Lung Allocation Score (LAS)• Discuss various statistics related to lung transplantation• Discuss decision making related to selection of single versus

double lung transplantation

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Indications for Referral

Is a Lung Transplant Indicated?

• Survival benefit?

• Quality of life benefit?

Would a lung transplant be beneficial?

• Single v. bilateral?

• Underlying comorbidities?• Age

• Frailty

• CAD, CRI

• DM, HTN...

Can the patient tolerate the transplant

surgery?

Slide Courtesy of Dr. David Roe Indiana University Lung Transplant Program

General Criteria

• Patients with chronic, end stage lung disease who meet all of the following general criteria:

– High (>50%) risk of death from lung disease within 2 years if lung transplantation is not performed

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

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

J Heart Lung Transplant 2015;34:1-15

Absolute Contraindications

• Recent history of malignancy. Generally 5 year disease-free interval is required

• Untreatable significant dysfunction of another major organ system (e.g. heart, liver, kidney, brain) unless combined organ transplantation can be performed

• Uncorrected atherosclerotic disease with suspected or confirmed end-organ ischemia or dysfunction and/or coronary artery disease not amenable to revascularization

• Acute medical instability, including but not limited to acute sepsis, myocardial infarction, liver failure


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• Uncorrectable bleeding diathesis• Chronic infection with highly virulent and/or resistant

microbes that are poorly controlled pre-transplant• Evidence of Mycobacterium tuberculosis infection• Significant chest wall or spinal deformity expected to

cause severe restriction after transplantation• Class II or III obesity (BMI ≥ 35.0 kg/m2)• Current non-adherence to medical therapy or history of

repeated or prolonged episodes of non-adherence to medical therapy that are perceived to increase the risk of non-adherence after transplantation



• Psychiatric or psychological conditions associated with the inability to cooperate with the medical/allied health care team and/or adhere with complex medical therapy

• Absence of an adequate or reliable social support system

• Severely limited functional status with poor rehabilitation potential

• Substance abuse or dependence. Serial blood and urine testing can be used to verify abstinence from substances of concern.


Relative Contraindications

• Age > 65 in association with low physiologic reserve and/or other relative contraindications

• Class I obesity (BMI 30.0 – 34.9 kg/m2), particularly truncal obesity

• Progressive or severe malnutrition• Severe, symptomatic osteoporosis• Extensive prior chest surgery with lung resection• Mechanical ventilation or ECLS• Colonization or infection with highly resistant or highly

virulent bacteria, fungi, and certain strains of mycobacteria (chronic extrapulmonary infection expected to worsen after transplantation)


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• Lung transplantation can be considered in patients with hepatitis B or C in those patients without significant clinical, radiographic, or biochemical signs of cirrhosis or portal hypertension and who are stable on appropriate therapy

• Lung transplantation can be considered in patients with HIV in those patients with controlled disease with undetectable HIV RNA and compliant on combined antiretroviral therapy. Candidates should have no current AIDS-defining illness



• Infection with Burkholderia cenocepacia, Burkholderiagladioli, and multidrug resistant Mycobacterium abscessus if the infection is sufficiently treated preoperatively and there is reasonable expectation for adequate control postoperatively

• Atherosclerotic disease burden sufficient to put the patient at risk for end-organ disease after lung transplantation

• In patients with CAD, patients may be candidates for percutaneous intervention, CABG preoperatively or CABG combined with lung transplantation

• Preoperative evaluation, degree of coronary artery disease deemed acceptable, and type of stent used (bare metal vs. DES) vary among transplant centers



• Other medical conditions that have not resulted in end-stage organ damage, such as diabetes mellitus, systemic hypertension, epilepsy, central venous obstruction, peptic ulcer disease, and GERD should be optimally treated before transplantation


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Previous Surgery

• Previous surgery is not a contraindication to lung transplantation

• Pleurodesis is most troublesome, but also is not a contraindication

• Pneumothorax in patients who may become future transplant candidates should be treated with the most effective immediate management. Management strategy is unlikely to affect future acceptance for transplantation

• Higher rates of bleeding, reexploration, and renal dysfunction are expected in patients with previous chest procedures. This may be a function of longer cardiopulmonary bypass times


Previous Surgery

• In otherwise well-selected candidates, medium-term and long-term outcomes are not affected by previous chest procedures

• In patients >65 years old with other comorbid conditions poorer outcomes are seen, and previous chest surgery should be taken into account during selection


Timing of referral for Lung Tplx • The evaluation process for transplantation is complex and time

consuming

• Risk of worsening lung disease and overall health

– Patient may become critically ill and the need for transplantation becomes urgent.

• Patients with a progressive lung disease should be referred to a transplant center when they are still able to undergo evaluation to determine the potential risks and benefits of lung transplantation in their case.

– Early referral may identify modifiable risk factors that would influence a patient's candidacy for transplantation or their outcome after transplantation.

• Factors that are timing restrictive include obesity, deconditioning, vaccination schedules, treatment of CAD


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Disease-Specific IndicationsTiming of Referral: ILD• Histopathologic or radiographic evidence of usual interstitial

pneumonitis (UIP) or fibrosing non-specific interstitial pneumonitis (NSIP), regardless of lung function.

• Abnormal lung function: forced vital capacity (FVC) <80% predicted or diffusion capacity of the lung for carbon monoxide (DLCO) <40% predicted.

• Any dyspnea or functional limitation attributable to lung disease.

• Any oxygen requirement, even if only during exertion.• For inflammatory interstitial lung disease (ILD), failure to

improve dyspnea, oxygen requirement, and/or lung function after a clinically indicated trial of medical therapy.


Disease-Specific IndicationsTiming of Referral: Cystic Fibrosis• FEV1 that has fallen to 30% or a patient with advanced

disease with a rapidly falling FEV1 despite optimal therapy (particularly in a female patient), infected with non-tuberculous mycobacterial (NTM) disease or B cepacia complex, and/or with diabetes.

• A 6-minute walk distance <400 m.• Development of pulmonary hypertension in the absence

of a hypoxic exacerbation (as defined by a systolic pulmonary arterial pressure (PAP) >35 mm Hg on echocardiography or mean PAP >25 mm Hg measured by right heart catheterization).


Disease-Specific IndicationsTiming of Referral: Cystic Fibrosis• Clinical decline characterized by increasing frequency of

exacerbations associated with any of the following:– An episode of acute respiratory failure requiring non-

invasive ventilation.– Increasing antibiotic resistance and poor clinical

recovery from exacerbations.– Worsening nutritional status despite

supplementation.– Pneumothorax.– Life-threatening hemoptysis despite bronchial

embolization.


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Disease-Specific IndicationsTiming of Referral: COPD• Disease is progressive, despite maximal treatment

including medication, pulmonary rehabilitation, and oxygen therapy.

• Patient is not a candidate for endoscopic or surgical LVRS. Simultaneous referral of patients with COPD for both lung transplant and LVRS evaluation is appropriate.

• BODE index of 5 to 6.

• PaCO2 >50 mm Hg or 6.6 kPa and/or PaO2 <60 mm Hg or 8 kPa.

• FEV1 <25% predicted.


Disease-Specific IndicationsTiming of Referral: Pulmonary Vascular Disease• NYHA Functional Class III or IV symptoms during

escalating therapy.

• Rapidly progressive disease (assuming weight and rehabilitation concerns not present).

• Use of parenteral targeted pulmonary arterial hyper-tension (PAH) therapy regardless of symptoms or NYHA Functional Class.

• Known or suspected pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis.


Lung Allocation Score (LAS)

• As of May 2005, each lung transplant candidate is assigned a Lung Allocation Score (LAS)

• The LAS is between 0-100

• The LAS was designed to facilitate allocation of the limited supply of donor organs to patients with more urgent need

• Despite the implementation of the LAS, up to 20% of patients annually will either be inactivated or die before an adequate donor becomes available

• Donor availability has not kept up with the increased number of patients in need of lung transplantation

J Pulmonar Respirat Med 2012;2:2

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• Overall median wait time for lung transplantation is less than 6 months

• Patients with LAS of at least 50 have a median wait time of about 1 month

• Between 2005 and 2012, there has been a 58% increase in patients with LAS of 35 or greater



• In the United States, the lung allocation policy prioritizes lung transplant candidates for lung offers by assigning them a LAS

• The LAS is used to prioritize waiting list candidates based on a combination of waitlist urgency and post-transplant survival– Waitlist urgency is what is expected to happen to a

candidate, given his or her characteristics, in the next year if a transplant is not received

– Post-transplant survival is what is expected to happen to a candidate , given his or her characteristics, in the fist year after transplant if a transplant is received

UNOS. A Guide to Calculating the Lung Allocation Score


• Calculating the LAS involves all of these very complex steps:

– Calculating the waiting list survival probability during the next year

– Calculate the waitlist urgency measure

– Calculate the post-transplant survival probability during the first post-transplant year

– Calculate the post-transplant survival measure

– Calculate the raw allocation score

– Normalize the raw allocation score to obtain the LAS

UNOS. A Guide to Calculating the Lung Allocation Score

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Lung Allocation ScorePart 1: Post transplant survival

FVC

PCWP ≥20

Continuous mechanical ventilation

Age

Serum creatinine

NYHA Functional class

Diagnosis

Part 2: Waiting list urgency

FVC

S-PAP, m-PAP, PCWP

Suppl.O2 required at rest

Age

BMI

Diabetes

Functional status

Six-minute walk distance

Continuous mech. ventilation

Diagnosis

pCO2

Transplant benefit = post transplant survival - waitlist survival.- The raw allocation score = transplant benefit (days) - waitlist survival (days).- The lung allocation score is derived by normalizing the raw allocation score to a range of 0 to 100.

Slide Courtesy of Dr. David Roe Indiana University

Selection of Donor Lungs• Extended donor criteria can be used, depending on

patient acuity, which can increase the donor pool and shortening waitlist times:– Donor age > 55– PaO2:FiO2 ratio < 300 mmHg– Abnormal chest radiograph– Donor tobacco use for >20 years– Evidence of aspiration– Presence of purulent secretions on bronchoscopy of

positive gram stain on lavage– Chest trauma or history of cardiopulmonary surgery


Other Factors Regarding Selection of Donor Lungs

• Donor and recipient size matching is important for adequate function of the transplanted organ as well as survival

• Donor and recipient ABO blood types and HLA compatibility (presence of panel reactive antibodies, PRA)

• Patients with high PRA, especially >25%, have increased 30 day and overall mortality


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Adult Lung TransplantsNumber of Transplants by Year and Procedure Type

5 6 32 69160

385

664

8741055

116012961305

14171445

14941635

1713

19031938

2138

2483

270628412907

3182

3462

3759 3752

4041 39904122

0

500

1000

1500

2000

2500

3000

3500

4000

4500

Nu

mb

er

of

Tra

nsp

lan

ts

Bilateral/Double Lung

Single Lung

NOTE: This figure includes only the adult lung

transplants that are reported to the ISHLT Transplant

Registry. As such, this should not be construed as

representing changes in the number of adult lung

transplants performed worldwide.2017

JHLT. 2017 Oct; 36(10): 1037-1079

Diagnosis SLT (N=18,207) BLT (N=36,046) TOTAL (N=54,253)

COPD 7,266 (39.9%) 9,539 (26.5%) 16,805 (31.0%)

IIP 6,449 (35.4%) 6,990 (19.4%) 13,439 (24.8%)

CF 218 (1.2%) 8,266 (22.9%) 8,484 (15.6%)

ILD-not IIP 1,078 (5.9%) 1,925 (5.3%) 3,003 (5.5%)

A1ATD 797 (4.4%) 1,912 (5.3%) 2,709 (5.0%)

Retransplant 922 (5.1%) 1,269 (3.5%) 2,191 (4.0%)

IPAH 88 (0.5%) 1,481 (4.1%) 1,569 (2.9%)

Non CF-bronchiectasis 67 (0.4%) 1,413 (3.9%) 1,480 (2.7%)

Sarcoidosis 312 (1.7%) 1,026 (2.8%) 1,338 (2.5%)

PH-not IPAH 135 (0.7%) 690 (1.9%) 825 (1.5%)

LAM/tuberous sclerosis 146 (0.8%) 381 (1.1%) 527 (1.0%)

OB 73 (0.4%) 395 (1.1%) 468 (0.9%)

CTD 140 (0.8%) 282 (0.8%) 422 (0.8%)

Cancer 7 (0.0%) 27 (0.1%) 34 (0.1%)

Other 509 (2.8%) 450 (1.2%) 959 (1.8%)

Adult Lung TransplantsIndications (Transplants: January 1995 – June 2016)

2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsProcedure Type within Indication, by Year

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

200

1

200

3

200

5

200

7

200

9

201

1

201

3

201

5

200

1

200

3

200

5

200

7

200

9

201

1

201

3

201

5

200

1

200

3

200

5

200

7

200

9

201

1

201

3

201

5

200

1

200

3

200

5

200

7

200

9

201

1

201

3

201

5

% o

f T

ran

sp

lan

ts

Bilateral/Double Lung Transplant Single Lung Transplant

A1ATD COPD IIP ILD-non IIP

2017JHLT. 2017 Oct; 36(10): 1037-1079

../Working_heartlung.ppt

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Adult Lung TransplantsMajor Indications by Year (%)

0

20

40

60

80

100

% o

f T

ran

sp

lan

ts

Transplant Year

COPD A1ATD CF IIP ILD-not IIP Retransplant

2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsMajor Indications by Year (Number)

0

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

Nu

mb

er

of

Tra

nsp

lan

ts

Transplant Year

COPD A1ATD CF IIP ILD-not IIP Retransplant

2017JHLT. 2017 Oct; 36(10): 1037-1079

Post-Transplant Survival and

Rejection

2017JHLT. 2017 Oct; 36(10): 1037-1079

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0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Su

rviv

al (%

)

Years

Bilateral/Double Lung (N=34,141)

Single Lung (N=18,926)

2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsKaplan-Meier Survival by Procedure Type for Primary

Transplant Recipients

Median survival (years):

Double Lung = 7.4; Conditional = 9.9

Single Lung = 4.6; Conditional = 6.4

p<0.0001

(Transplants: January 1990 – June 2015)

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Su

rviv

al (%

)

Years

1990-1998 (N=9,797)

1999-2008 (N=21,665)

2009-6/2015 (N=24,145)

2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsKaplan-Meier Survival by Era


1990-1998: 4.2; Conditional=7.1;

1999-2008: 6.1; Conditional=8.5;

2009-6/2015: NA; Conditional=NA

1990-1998 vs. 1999-2008: p<0.0001;

1990-1998 vs. 2009-6/2015: p<0.0001;

1999-2008 vs. 2009-6/2015: p<0.0001


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Su

rviv

al (%

)

Years

A1ATD (N=3,117) CF (N=8,381) COPD (N=17,098)

IIP (N=12,710) ILD-not IIP (N=2,730) Retransplant (N=2,226)

2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsKaplan-Meier Survival by Diagnosis

All pair-wise comparisons were

significant at p < 0.05 except

A1ATD vs. ILD-non IIP and COPD

vs. ILD-non IIP


A1ATD: 6.7; CF: 9.2; COPD: 5.8; IIP:

4.9; ILD-not IIP: 6.0; Retransplant: 2.9


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0

10

20

30

40

50

Overall(N=17,058)

18-34(N=2,119)

35-49(N=2,553)

50-59(N=4,985)

60-65(N=4,608)

66+(N=2,793)

Female(N=7,133)

Male(N=9,925)

% e

xp

eri

en

cin

g r

eje

cti

on

wit

hin

1 y

ea

r

Analysis is limited to patients who were alive at the time

of the follow-up. No rejection = Recipient had (1) no acute rejection

episodes and (2) was reported either as not hospitalized

for rejection or did not receive anti-rejection agents.2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsPercentage Experiencing Any Rejection between Discharge

and 1-Year Follow-Up

No pair-wise comparisons were significant at < 0.05

except 18-34 vs. all other age groups

(Follow-ups: July 2004 – June 2016)

Functional and Employment Status

and Rehospitalization Post

Transplant

2017JHLT. 2017 Oct; 36(10): 1037-1079

0%

20%

40%

60%

80%

100%

1 Year (N = 11,203) 2 Year (N = 9,348) 3 Year (N = 7,879)

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsFunctional Status of Surviving Recipients

(Follow-ups: January 2009 – June 2016)

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2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsSurviving Recipients Working Post-Transplant


0%

10%

20%

30%

40%

50%

1 Year (N=9,751) 3 Years (N=6,711) 5 Years (N=4,642)

0%

20%

40%

60%

80%

100%

Up to 1 Year(N = 12,887)

Between 2-3 Years(N = 8,912)

Between 4-5 Years(N = 6,270)

Hospitalized, Rejection + Infection Hospitalized, Infection Only

Hospitalized, Rejection Only Hospitalized, Not Rejection/Not Infection

No Hospitalization

2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsRehospitalization Post Transplant of Surviving Recipients


Single vs Bilateral/Double Lung Transplant

• The subject of a great deal of debate

• Short and long term outcomes are to be considered

• Individual and societal benefits also must be considered

• SLT maximizes benefit to society by transplanting 2 candidates per donor

• DLT maximizes benefit to the individual

• No high quality evidence comparing these 2 approaches

• Practice patterns are often institution specific

Thorac Surg Clin 2015;25(1):47-54

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Single vs Bilateral/Double Lung Transplant

Thorac Surg Clin 2015;25(1):47-54

0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Su

rviv

al (%

)

Years


Single Lung (N=18,926)

2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsKaplan-Meier Survival by Procedure Type for Primary

Transplant Recipients


Double Lung = 7.4; Conditional = 9.9

Single Lung = 4.6; Conditional = 6.4

p<0.0001


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Su

rviv

al (%

)

Years

Single lung (N=1,136)


2017JHLT. 2017 Oct; 36(10): 1037-1079

Adult Lung TransplantsKaplan-Meier Survival by Procedure Type

Diagnosis: A1ATD

p<0.0001


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0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Su

rviv

al (%

)

Years



2017JHLT. 2017 Oct; 36(10): 1037-1079


Diagnosis: COPD

p<0.0001


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Su

rviv

al (%

)

Years


Bilateral/Double Lung lung (N=6,293)

2017JHLT. 2017 Oct; 36(10): 1037-1079


Diagnosis: IIP

p<0.0001


0

25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Su

rviv

al (%

)

Years



2017JHLT. 2017 Oct; 36(10): 1037-1079


Diagnosis: ILD-not IIP

p<0.0001


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Indications for Referral

Is a Lung Transplant Indicated?

• Survival benefit?

• Quality of life benefit?

Would a lung transplant be beneficial?

• Single v. bilateral?

• Underlying comorbidities?• Age

• Frailty

• CAD, CRI

• DM, HTN...

Can the patient tolerate the transplant

surgery?


Objectives

• Understand general criteria for patient selection for lung transplantation

• Discuss absolute and relative contraindications for lung transplantation

• Understand how previous surgery and treatment for pneumothorax affects a patient’s candidacy for lung transplantation

• Understand disease-specific indications for lung transplantation

• Discuss the Lung Allocation Score (LAS)• Discuss various statistics related to lung transplantation• Discuss decision making related to selection of single versus

double lung transplantation

Thank you for your attention!!!

Documents

PowerPoint Presentation · 9/20/2018 1 Lung Diseases and Criteria Leading to Transplant Roger F. Johnson, MD, FCCP Pulmonary and Critical Care Medicine St. Vincent Evansville Medical