01

Jonathan V. Todd, PhD1; Wayne J. Morgan, MD2; Rhonda D. Szczesniak, PhD3; Josh S. Ostrenga, MS1; Oisin J. O’Connell, MD4; Elizabeth A. Cromwell, PhD1; Albert Faro, MD1, Raksha Jain, MD5

1 Cystic Fibrosis Foundation, Bethesda, MD.

2 Department of Pediatrics, The University of Arizona, Tucson, AZ.

3 Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.

4 Department of Respiratory Medicine, Cork University Hospital, Cork, Ireland.

5 Department of Medicine, University of Texas Southwestern.

Rationale:

Declines in percent predicted Forced Expiratory Volume in 1 Second (ppFEV1) are an important marker of clinical progression of Cystic Fibrosis (CF).

Objectives: We examined ppFEV1 variability on a combined outcome of lung transplant or death.

Methods: 

We estimated the association between ppFEV1 variability and the combined outcome of lung transplant or death. We included children ages 8 years and above with CF and two prior years of ppFEV1 data before baseline between 2005 and 2021. We defined ppFEV1 increased variability as any relative increase or decrease of at least 10% in ppFEV1 from a two-year averaged baseline. A marginal structural Cox proportional hazards model was used. We examined a cumulative measure of ppFEV1 variability, defined as the cumulative proportion of visits with ppFEV1 variability at each visit. Kaplan-Meier survival curves were generated based upon quartiles of the cumulative distribution of ppFEV1 variability.

Measurements and main results: 

We included 9,706 CF patients in our cohort. Median age at cohort entry was 8.3 (IQR 8.2-8.4) years, 50% of patients were female, 94% white, and median baseline ppFEV1 was 94.4 (IQR 81.6-106.1). The unadjusted HR for increased ppFEV1 variability on lung transplant/mortality was 4.13 (95% CI 3.48-4.90) and the weighted HR was 1.49 (95% CI 1.19-1.86). Survival curves stratified by quartile of cumulative variability demonstrated an increased hazard of lung transplant/mortality as the proportion of cumulative ppFEV1variability

increased.

Conclusions: 

We found a strong association between ppFEV1 variability and lung transplant or mortality in a cohort of people with CF in the US.

[CITATION]: Todd JV, Morgan WJ, Szczesniak RD, et al. FEV1 Variability Predicts Lung Transplant or Mortality in Cystic Fibrosis Patients in the US. Ann Am Thorac Soc. 2024 Jun 18.  

[DOI]: 10.1513/AnnalsATS.202307-648OC

[IF]: 6.8

02

P Pradere1, J Le Pavec2, S Morisset3, V Gerovasili4, R Kessler5, A Adlakha6, V Bunel7, K Santhanakrishnan8, X Demant9, A Roux10 , L Falque11 , V Cottin12 , J Parmar13, M Reynaud-Gaubert14, T Villeneuve15, A Tissot16, O Mercier17, A J Fisher18

1 Pneumology Department, Marie Lannelongue Hospital, Le Plessis Robinson, France; Newcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, United Kingdom.

2 Pneumology Department, Marie Lannelongue Hospital, Le Plessis Robinson, France; Paris Saclay University, Faculty of Medical Sciences, Le Kremlin-Bicêtre, France; INSERM UMR-S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies, Hôpital Marie Lannelongue, Le Plessis Robinson, France.

3 Independent Biostatistician, Pérouges, France.

4 Transplant Department, Royal Brompton and Harefield Hospitals Guy's and St. Thomas' National Health Service Foundation Trust, London, United Kingdom; Imperial College London, Faculty of Medical Sciences, London, United Kingdom.

5 Groupe de Transplantation Pulmonaire des Hôpitaux Universitaires de Strasbourg, Inserm-Université de Strasbourg, Strasbourg, France.

6 Transplant Department, Royal Free London NHS Foundation Trust, University Hospitals Birmingham, Birmingham, United Kingdom.

7 APHP, Nord-Université Paris Cité, Hôpital Bichat-Claude Bernard, Service de Pneumologie B et Transplantation Pulmonaire, Paris, France.

8 Transplant Department, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom.

9 Hôpital Haut-Lévêque, Service de pneumologie, CHU de Bordeaux, Bordeaux, France.

10 Hôpital Foch, Service de pneumologie, Suresnes, France.

11 Service Hospitalier Universitaire Pneumologie et Physiologie, Pôle Thorax et Vaisseaux, CHU Grenoble Alpes, Grenoble, France.

12 Hospices Civils de Lyon, GHE, Service de Pneumologie, Inserm, Lyon, France.

13 Transplant Department, Royal Papworth Hospital, Cambridge, United Kingdom.

14 CHU de Marseille, APHM, Hôpital Nord, Service de Pneumologie et Équipe de Transplantation pulmonaire; Aix-Marseille Université, Marseille, France.

15 CHU de Toulouse, Hôpital Larrey, Toulouse, France.

16 Nantes Université, CHU Nantes, Service de Pneumologie, Institut du thorax, Nantes, France.

17 Paris Saclay University, Faculty of Medical Sciences, Le Kremlin-Bicêtre, France; INSERM UMR-S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies, Hôpital Marie Lannelongue, Le Plessis Robinson, France; Thoracic Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Le Plessis Robinson, France.

18 Newcastle University Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, United Kingdom; Institute of Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.

Background:

The age profile of organ donors and patients on lung transplantation (LT) waiting lists have changed over time. In Europe, the donor population has aged much more rapidly than the recipient population, making allocation decisions on lungs from older donors common. In this study we assessed the impact of donor and recipient age discrepancy on LT outcomes in the UK and France.

Methods: 

A retrospective analysis of all adult single or bilateral LT in France and the UK between 2010 and 2021. Recipients were stratified into 3 age author groups: young (≤30 years), middle-aged (30-60) and older (≥60). Their donors were also stratified into 2 groups <60, ≥60. Primary graft dysfunction (PGD) rates and recipient survival was compared between matched and mismatched donor and recipient age groups. Propensity matching was employed to minimize covariate imbalances and to improve the internal validity of our results.

Results: Our study cohort was 4,696 lung transplant recipients (LTRs). In young and older LTRs, there was no significant difference in 1 and 5-year post-transplant survival dependent on the age category of the donor. Young LTRs who received older donor grafts had a higher risk of severe grade 3 PGD.

Conclusions: 

Our findings show that clinically usable organs from older donors can be utilized safely in LT, even for younger recipients. Further research is needed to assess if the higher rate of PGD3 associated with use of older donors has an effect on long-term outcomes.

[CITATION]：Pradere P, Le Pavec J, Morisset S, et al. Donor to recipient age matching in lung transplantation:A European experience.J Heart Lung Transplant.2024 Jun 21:S1053-2498(24)01700-5.

[DOI]: 10.1016/j.healun.2024.06.008.

[IF]: 6.4