Prof Geert M. Verleden UZ Gasthuisberg Leuven

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1 Prof Geert M. Verleden UZ Gasthuisberg Leuven

2 Patients with chronic end-stage lung disease, such as COPD, CF, PAH, Pulmonary fibrosis Max y for HLTx y for LTx Failing medical treatment Or no medical treatment exists Need for Information Demonstration of adequate health behavior Willingness to adhere to guidelines Aim of LTx: survival benefit and increase in QOL

3 Malignancy in the last 2 years, except cutaneous squamous and basal cell tumors Remains questionnable regarding for instance breast cancer, renal cancer. How long tumor free? Untreatable advanced dysfunction of other organs (kidney, liver, ) Unless combined transplantation Untreatable coronary artery disease What is nowadays untreatable? Non-curable chronic extrapulmonary infections (hep B, hep C, HIV) Also questionnable

4 Significant chest wall/spinal deformity To be discussed with surgeons Documented non-adherence Specific problem in young CF patients Untreatable psychiatric or psychologic condition with inability to comply with medical therapy Absence of social support Difficulties to adhere to strict follow up protocols Substance addiction: tobacco, alcohol, narcotics, drug abuse that is active or within the last 6 months Is six months enough delay?

5 Age > 65 y Critical or unstable clinical condition (invasive ventilation, ECMO) BMI > 30 Colonization with highly resistant or virulent bacteria, fungi or mycobacteria CF patients specifically Mycobacterial colonization/infection remains problematic arterial hypertension peptic ulcer GER (50% or more pretx) Severe or symptomatic osteoporosis Diabetes Should be adequately treated before Tx

6 Number of Transplants Bilateral/Double Lung Single Lung 1990 UZ Leuven J Heart Lung Transplant 2010;29:

7 Number Lung Transplantations per year in UZ Leuven

8 Increasing number of referrals Increasing number of accepted donors Increasing number of transplant procedures Decreasing waiting list mortality

9 Lung Transplantations per year in UZ Leuven Number > 50/y

10 Number of centers Percentage of transplants Average number of lung transplants per year Number of centers Percentage of transplants J Heart Lung Transplant 2010;29:

11

12 (HEART)-LUNG Tx IN LEUVEN BY DISEASE (n = 766) 5% 23% 3% 2% 2% 4% 6% 14% 42% alpha1 ATD emphysema cystic fibrosis PH Eisenmenger ReTx Fibrosis Bronchiectasis miscellaneous

13 < >60 age distribution

14 (N=4,392) (N=6,726) /2005 (N=9,419) Survival (%) ISHLT 2007 Years J Heart Lung Transplant 2007;26:

15 (N=4,392) (N=6,726) /2005 (N=9,419) Leuven Survival (%) ISHLT 2007 Years J Heart Lung Transplant 2007;26: Verleden et al; Clinical Transplants 2007.

16 75% 60%

17 Survival evolution in Leuven 5-y survival

18 Leuven 100 ISHLT Alpha-1 (N=2,187) CF (N=4,144) COPD (N=9,616) IPF (N=5,459) IPAH (N=1,123) Sarcoidosis (N=660) 75 HALF-LIFE Alpha-1: 6.1 Years; CF: 7.1 Years; COPD: 5.2 Years; IPF: 4.3 Years; IPAH: 4.9 Years; Sarcoidosis: 5.1 Years Survival (%) Survival comparisons All comparisons with Alpha-1 and CF are statistically significant at IPAH vs. IPF: p = COPD vs. IPF: p < Years P=0.0021

19 Increasing experience Increase in number of transplantations per year Use of marginal donors Use of non-heart beating donors (DCD donors) Use of euthanasia donors

20 Age > j Smokers (> 10 py) PaO2 < 400 mm Hg Chest X-ray with infiltrates Purulent secretions

21

22 Meers et al. Transpl Int. 2010;23:

23 NHBD De Vleeschauwer et al. JHLT 2011( n=21) Van de Wauwer et al. Eur J CardioThorac Surg. 2011; (n=27)

24 Increasing experience Increase in number of transplantations per year Use of marginal donors Use of non-heart beating donors (DCD donors) Shift from single to double lung transplantation

25 HLTx SLtx SSLTx 45 91%

26

27 Increasing experience Increase in number of transplantations per year Use of marginal donors Use of non-heart beating donors (DCD donors) Shift from single to double lung transplantation Specific follow up in Leuven

28 Outpatient clinic run by specialized nurses, supervised by staff members of transplant unit Every year global check up during short admission All complications treated in own transplant unit in Leuven (role of experience!!)

29 Increasing experience Increase in number of transplantations per year Use of marginal donors Use of non-heart beating donors (DCD donors) Shift from single to double lung transplantation Specific follow up in Leuven Cooperation with GP/specialist

30 Calcineurin inhibitor Ciclosporine or tacrolimus Proliferator inhibitor Azathioprine or mycophenolate corticosteroids

31 Macrolides clarithomycin Antifungal drugs Itraconazole, voriconazole, fluconazole NSAID Ibuprofen and others Antihistamines Antidepressants

32 Increasing experience Increase in number of transplantations per year Use of marginal donors Use of non-heart beating donors (DCD donors) Shift from single to double lung transplantation Specific follow up in Leuven Cooperation with GP/specialist Better treatment options for chronic rejection

33 FEV1, L 4 3,5 3 2,5 2 1,5 1 0,5 0 07/01/ /05/ /09/ /01/ /05/ /09/ /01/ /05/ /09/ /01/ /05/ /09/ /01/2006 Postoperative time

34

35 Vos R et al. Eur Respir J 2011; 37:

36 active placebo P=0.0025

37 ESW ratg FK + MMF BOS 2 75% ratg Neutrophils in BAL Time after HLTx Verleden et al. Eur Respir J 2005; 25:

38 ESW FEV1 ratg FK + MMF ratg Time after HLTx

39 Verleden et al. Transpl Int 2011; 24:

40 P=0.028

41 Freedom from BOS % 53% Months post transplantation ISHLT Leuven

42 Number of Tx procedures is imperative for good results More SSLTx Use of marginal and NHB donors Results of lung transplantation have significantly increased in recent years Expertise of a whole team is extremely important Close follow up is evenly important Chronic rejection remains the major cause of death Role of azi in prevention/treatment ofchronic rejection (35-40% responders) Trying to stabilize FEV 1 decline with MLK

43

44 Medics Robin Vos Lieven Dupont Dirk Van Raemdonck Marion Delcroix Jonas Yserbyt Leuven pulmonology and surgical team Erik Verbeken (pathology) Tx Nurses Kristel Jans Kris Rosseel Veronique Schaevers Mieke Meelberg Annemieke Schoonis E 650 paramedics BOF-ZAP researcher Bart Vanaudenaerde PhD Students Kathleen Blondeau Veerle Mertens Nele Geudens Stéphanie Devleeschauwer Caroline Meers Shana Wouters Stijn Verleden David Ruttens, Elly Vandermeulen

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