Lung transplantation has become an established treatment for end-stage lung diseases such as cystic fibrosis (CF). According to the document, lung transplantation for CF has seen improved outcomes over time, with 1-year survival rates now over 97% and 3-year survival rates of 86% at one center. While lung transplantation can significantly extend life for patients with CF, it also carries risks such as infections, rejection, and complications from immunosuppression. Ongoing research continues to further improve outcomes for CF patients receiving lung transplants.

2. Lung Transplantation for Cystic Fibrosis
Reda E. Girgis, MD
Medical Director, Lung Transplantation
Director, Pulmonary Hypertension Clinic
Richard DeVos Heart and Lung Transplant Program
Professor of Medicine, MSU College of Human Medicine

3. Adult Lung Transplants
Number of Transplants by Year and Procedure Type
5 6 32 69
160
385
664
874
1055
11601296
1305
1417
1445
1494
16351713
19031938
2138
2483
2706
28412907
3182
3462
3759 3752
40413990
4122
0
500
1000
1500
2000
2500
3000
3500
4000
4500
NumberofTransplants
Bilateral/Double Lung
Single Lung
2017
JHLT. 2017 Oct; 36(10): 1037-1079
US: 2345 in 2016 (highest ever),
c/w 1,085 in 2003

4. Adult Lung Transplants
Major Indications by Year (%)
0
20
40
60
80
100
%ofTransplants
Transplant Year
COPD A1ATD CF IIP ILD-not IIP Retransplant
2017
JHLT. 2017 Oct; 36(10): 1037-1079

5. Lung Allocation Score (LAS)
Diagnosis Groups
Group A: obstructive lung disease: COPD
Group B: Pulmonary vascular disease (PAH)
Group C: Cystic Fibrosis
Group D: Restrictive Lung disease: IPF

6. LTX in US by Diagnosis Group

7. Median Time to Transplant
Valapour M. SRTR annual report 2016. Am J Transplant 2018; 18, Sup 1

8. Why?
 New Lung Allocation Policy (U.S.)
 More donor lungs
• Better management and utilization
• Expanded criteria
• New options
 Expanded recipient criteria

9. UNOS Lung Allocation System
Benefit = 1yr Post-transplant survival – 1 yr Waitlist
survival
Score = Benefit – waitlist survival = PT survival – 2
x WL survival
Egan TM. Am J Transplant 2006
Waitlist Survival Post-tx survival

10.  Lung diagnosis
 Age
 FVC (Gp D)
 Oxygen use
 Assisted ventilation
 Functional status
 PASP
 BMI (<20)
 6 MWD
 Diabetes
 Cardiac index (<2)
 CVP (Gp B > 7)
 Serum creatinine and
increase in creatinine
 PaCO2 and rise
 Bilirubin and rise
LAS Calculator (revised 2/15)
(http://optn.transplant.hrsa.gov/converge/resources/allocationcalculators)

11. DISTRIBUTION OF NON-ZERO LAS FOR ACTIVE LUNG AND
HEART-LUNG REGISTRATIONS (12+) BY DIAGNOSIS GROUP
On July 23, 2010
34.6
32.9
34.3
37.0
40.1
30
35
40
45
50
55
60
All (N=1300) A (N=638) B (N=111) C (N=142) D (N=408)
LAS
Squares represent median LAS;
bars include 10th to 90th %-iles

12. 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
Survival(%)
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)
2017
JHLT. 2017 Oct; 36(10): 1037-1079
Adult Lung Transplants
Kaplan-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
Median survival (years):
A1ATD: 6.7; CF: 9.2; COPD: 5.8; IIP:
4.9; ILD-not IIP: 6.0; Retransplant: 2.9
(Transplants: January 1990 – June 2015)

13. 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
Survival(%)
Years
A1ATD (N=2,441) CF (N=6,771)
COPD (N=13,708) IIP (N=9,309)
ILD-not IIP (N=2,027) Retransplant (N=1,424)
2017
JHLT. 2017 Oct; 36(10): 1037-1079
Adult Lung Transplants
Kaplan-Meier Survival by Diagnosis Conditional on
Survival to 1 Year
Median survival (years): A1ATD: 8.9; CF: 12.0; COPD:
7.2; IIP: 7.1; ILD-not IIP: 8.1; Retransplant: 6.5
All pair-wise comparisons were
significant at p < 0.05 except A1ATD vs.
ILD-non IIP, COPD vs. IIP, COPD vs.
Retransplant and IIP vs. Retransplant
(Transplants: January 1990 – June 2015)

14. 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
Survival(%)
Years
1990-1998 (N=1,343)
1999-2008 (N=3,386)
2009-6/2015 (N=3,549)
2017
JHLT. 2017 Oct; 36(10): 1037-1079
Adult Lung Transplants
Kaplan-Meier Survival by Procedure Type and Era
Diagnosis: CF, Bilateral/Double Lung
1990-1998 vs. 1999-2008: p<0.0001
1990-1998 vs. 2009-6/2015: p<0.0001
1999-2008 vs. 2009-6/2015: p = 0.0021
(Transplants: January 1990 – June 2015)

15. Indications for Lung Transplantation
Severe end-stage lung disease with
expected 2-3 yr survival < 50%
Absence of significant extra-pulmonary
organ dysfunction
High likelihood of surviving 90 d and 5
years from general medical perspective
if graft function adequate
Psychosocial considerations
 Motivation; Compliance
 Adequate social support ISHLT Consensus 2014

16. Indications for Transplant
Referral in Cystic Fibrosis
FEV1 < 30% of predicted or rapid decline,
especially in females
Increasing frequency of and severity of
exacerbations
Refractory and recurrent pneumothorax or
hemoptysis
Hypoxemia requiring supplemental oxygen
Hypercapnia
Pulmonary hypertension
Orens JB et al. JHLT 2006

17. Predictors of Survival
• 3340 pts FEV1 < 30% in
CFFPR, 2003 - 13
• 37% died, 29% Tx
• 61% of deaths not referred
• Sig MV predictors (HR):
• Female – 1.55
• BMI ≤ 18 – 1.57
• Unknown genotype – 1.86
• Exacerbations (≥1/y) – 1.71
• > 4: 2 yr median survival
• O2 use – 2.08 (med surv:3.1y)
• B cepacia – 1.81
• CFRD – 1.44
• Married – 0.71
After FEV1 < 30%
Ramos KJ. Chest 2017; 151:1320
Among waitlisted subjects, LTX
conferred 69% reduction in risk
of death with greater benefit
the higher the LAS *
* Thabut G. AJRCCM 2013

18. Waitlist Mortality

19. Referral of CF to Transplant
CFFPR analysis of 1240 pts with FEV1 <30%
for 2 consecutive years
35% not referred
Multivariate analysis of predictors
 Medicaid insurance: 1.79
 Age (per 5 yr increase): 1.25
 Non HS graduate: 2.27
 B cepacia: 2.48
 Exacerbations, O2 use associated with referral
Ramos KJ. J Cystic Fibrosis 2016;15:196

20. Lung Transplant Complications
Peri-Operative (30 d)
 Primary Graft Dysfunction (PGD)
 Hemorrhage
Early (1 – 6 m)
 Infection: bacterial, viral (CMV), fungal
 Acute rejection
 Bronchial stenosis, diaphragmatic paresis
Late
 Chronic Renal Insufficiency
 Malignancy
 Obliterative Bronchiolitis (CLAD)

21. Infection Considerations in CF
Pan-resistant Pseudomonas: no effect on outcome
MRSA: no clear impact
B cenocepacia (1yr surv: 68 vs. 94%); gladioli, dolosa
also worse outcome; multivorans, others no difference)
Fungal Infections
 Peri-operative prophylaxis/treatment for aspergillus
 Large mycetoma with pleural thickening
 Scedosporium prolificans considered contraindication
NTMB colonization
 Peri-operative Rx/prophylaxis
 M. abscessus considered contraindication
Dupont L. Curr Opin Pulm Med 2017; 23:574

22. Post-tx Co-morbidities in CF
CF related diabetes
Renal disease
Osteopenia/Osteoporosis
Hypertension
CF associated liver disease
Malignancy
Jardel S. Clinical Transplant 2018

23. New Onset Diabetes Mellitus in Patients Receiving Calcineurin Inhibitors: A Systematic Review and Meta‐Analysis
New Onset Diabetes Mellitus in Patients Receiving Calcineurin Inhibitors: A Systematic Review and Meta‐Analysis, Volume: 4, Issue: 4, Pages: 583-595, First published: 25
February 2004, DOI: (10.1046/j.1600-6143.2003.00372.x)
More localization of FKBP-12 vs. cyclophilin to beta cells

24. Hayes D. JTCVS 2015
Waitlist survival
Post transplant survival
CFRD does not impact post
transplant survival

25. Renal Function Post Tx in CF
N=933 with
pre-tx eGFR >
60
58% with ≥
stage 3 CKD
by 5 yrs
(eGFR < 60)
12% stage V
(eGFR < 15)
Risks: age,
female, CFRD,
pre-tx GFR 60-
90
Quon BS. Chest 2012; 142:185

26. Cancer in CF Post LTx
17-27 fold increase in digestive cancers
Colonoscopy recommended at age 30 – 35
Higher likelihood of EBV negative recipient
increases risk of mismatch and post-
transplant lymphoproliferative disorder
(PTLD)
Skin cancer risk with voriconazole use

27. Other Considerations in CF
Nutritional status
 Increased risk with BMI < 18
GE dysmotility
DIOS
Chronic Sinusitis
Psychosocial issues, compliance

28. Lung Transplantation at Spectrum Health
1st Tx: Feb, 2013
CMS Jan, 2014
BDCT Jan, 2018
111 transplanted
1 yr survival: 97%
3 yr survival: 86%
Many higher risk
patients turned down
elsewhere
12 CF; 1 death at 2 yr

29. 100th Lung Transplant Recipient at
Spectrum Health: Christmas Eve, 2017
WOOD TV-8
Pre-Tx FEV1: 12% (< 30% for 6 yrs)
5 m post Tx: 103%

30. 30
SRTR Report Jan. 2018:Transplants performed 7/14 – 12/16; N = 57
Expected deaths: 6
Observed: 0
HR: 0.25
95% CI: 0.03 – 0.69
1 of 5 centers in US
with better than
expected 1 yr
Survival
Also, higher than
expected transplant
rates
SRTR.org

31. CF Research Program in GR
Collaborative effort between SH and MSU
Funding by MSU, SH/MSU Alliance and Hunt
for the Cure (huntforacure.com)
Personnel
 Senior investigator: MSU Global impact initiative
(GII) in precision medicine
 Basic scientist based at GRRC
 Physician-Scientist
 Adult and pediatric CF; lung transplant, ILD, PH
 Fall 2018

32. 3.7 years post; FEV1: 86%; eGFR: 59