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

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.

International experience with conversion from cyclosporine to tacrolimus for acute and chronic lung allograft rejection.

OBJECTIVE: A retrospective study involving 13 institutions was performed to assess the efficacy of conversion from cyclosporine (INN: ciclosporin) to tacrolimus. METHODS: Data from 244 patients were analyzed. Indications for conversion were recurrent-ongoing rejection (n = 110) and stage 1 to 3 bronchiolitis obliterans syndrome (n = 134). RESULTS: The incidence of acute rejection decreased significantly within 3 months after versus before the switch from cyclosporine to tacrolimus (P <.01). For patients with recurrent-ongoing rejection, the forced expiratory volume in 1 second decreased by 1.96% of predicted value per month (P =.08 vs zero slope) before and increased by 0.34% of predicted value per month (P =.32 vs zero slope) after conversion (P <.06). For patients with stage 1 to 3 bronchiolitis obliterans syndrome, a significant reduction of rejection episodes was observed (P <.01). In single transplant recipients a decrease of the forced expiratory volume in 1 second averaged 2.25% of predicted value per month (P <.01 vs zero slope) before and 0.29% of predicted value per month after conversion. Corresponding values for bilateral transplant recipients were 3.7% of predicted value per month (P <.01 vs zero slope) and 0.9% of predicted value per month (P = 0.04 vs zero slope), respectively. No significant difference in the incidence of infections within 3 months before and after conversion was observed. CONCLUSIONS: Conversion from cyclosporine to tacrolimus after lung transplantation is associated with reversal of recurrent-ongoing rejection. Conversion for bronchiolitis obliterans syndrome allows short-term stabilization of lung function in most patients.