Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation.

Angela Koutsokera,Sacha Mussot,Christiane Knoop,Christophe Pison,Jean P Antonietti,Paola M Soccal,Antoine Roux,Carine Gomez,Christian Benden,Andreas Fritz,Romain Kessler,Johanna Claustre,Hervé Mal,Marcel Dahan,A N Tissot ,A Magnan ,Édouard Sage ,K Botturi ,R Guillemain ,Martine Reynaud‐Gaubert ,John‐David Aubert ,Jean‐François Mornex ,C Dromer ,Pierre‐Joseph Royer ,Laurent Nicod

doi:10.3389/fmed.2017.00109

Abstract

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. 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. 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. 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.

Highlights

Chronic lung allograft dysfunction (CLAD) is the principal cause of poor long-term survival in lung transplantation (LT) and, no international consensus definition has been developed to date, CLAD refers to the persistent decline of the forced expiratory volume in one second (FEV1) that cannot be attributed to a specific cause other than chronic graft rejection [1, 2]
For restrictive allograft syndrome (RAS), various diagnostic criteria have been used in different studies, but overall, RAS is characterized by a restrictive ventilation defect and radiological signs of fibrosis or infiltrates [7,8,9]
Cohort of LT (COLT) and Swiss Transplant Cohort Study (STCS) patients were eligible for 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

Summary

Introduction

Chronic lung allograft dysfunction (CLAD) is the principal cause of poor long-term survival in lung transplantation (LT) and, no international consensus definition has been developed to date, CLAD refers to the persistent decline of the forced expiratory volume in one second (FEV1) that cannot be attributed to a specific cause other than chronic graft rejection [1, 2]. Bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) are considered to be the two main phenotypes of CLAD [2, 3]. BOS is characterized by persistent airflow obstruction in the absence of a restrictive ventilation defect and imaging studies that may be unremarkable or show air trapping [4]. Early-onset BOS, developing within 2 or 3 years after LT, is associated with unfavorable outcomes, resulting in high morbidity and mortality soon after LT [5, 6]. 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 inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described

Methods

Results

Conclusion