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

Abstract

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.

Keywords: bronchiolitis obliterans syndrome; chronic lung allograft dysfunction; chronic rejection; predictive model; restrictive allograft syndrome.

Figure 1

Flow chart diagram of the evaluated population.

Figure 2

(A) Receiver operating characteristic (ROC) analysis of the best performing model for the prediction of early-onset chronic lung allograft dysfunction after adjusting for center effect [area under the curve (AUC) = 0.766, SE = 0.0325, 95% CI 0.703–0.830]. (B) ROC curve of the model, with and without the parameter of “Y1 class II DSA” (AUC 0.766 vs. 0.730, respectively, p = 0.074).

Figure 3

Probabilities of stability, bronchiolitis obliterans syndrome (BOS), and restrictive allograft syndrome (RAS) calculated for all modalities of each significant independent variable for the studied population (n = 230).