Development of a multivariate prediction model for early-onset bronchiolitis obliterans syndrome and restrictive allograft syndrome in lung transplantation

Angela Koutsokera (1) , Pierre J. Royer (2) , Jean P. Antonietti (1) , Andreas Fritz (3) , Christian Benden (4) , John D. Aubert (1) , Adrien Tissot (5, 2) , Karine Botturi (5, 2) , Antoine Roux (5) , Martine L. Reynaud-Gaubert , Romain Kessler (6) , Claire Dromer (7) , Sacha Mussot (8) , Herve Mal (9) , Jean-Francois Mornex (10) , Romain Guillemain (11) , Christiane Knoop (11) , Marcel Dahan (12) , Paola M. Soccal (13) , Johanna Claustre (14) , Edouard Sage (5) , Carine Gomez (5) , Antoine Magnan (2) , Christophe Pison (15, 16) , Laurent P. Nicod (1) , Kian Fan Chung , Mark Wewers , Gunnar N Hillerdal

1 Division of Pulmonary Medicine
2 ITX - ITX - unité de recherche de l'institut du thorax
3 Biomax Informatics AG
4 Division Pulmonary Medicine
5 LOBIP - Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique
6 Lung Transplantation Center
7 Service Maladies Respiratoires
8 Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire
9 INSERM UMR1152, Service de Pneumologie et Transplantation Pulmomaire
10 RPC - Rétrovirus et Pathologie Comparée
11 Department of Chest Medicine
12 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
13 Division Pulmonary Medicine
14 Clinique Universitaire de Pneumologie, Pôle Thorax et Vaisseaux
15 LBFA - Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée
16 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]

Background: Chronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described. Methods: LT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis. Results: Among patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS. Conclusion: Although these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach.

Mots clés: predictive model; restrictive allograft syndrome; bronchiolitis obliterans syndrome; chronic lung allograft dysfunction; chronic rejection

Domaines: Sciences du Vivant [q-bio]

Angela Koutsokera, Pierre J. Royer, Jean P. Antonietti, Andreas Fritz, Christian Benden, et al.. Development of a multivariate prediction model for early-onset bronchiolitis obliterans syndrome and restrictive allograft syndrome in lung transplantation. Frontiers in Medicine, 2017, 4, ⟨10.3389/fmed.2017.00109⟩. ⟨hal-01608943⟩