Human leukocyte antigen mismatching and survival after lung transplantation in adult and pediatric patients with cystic fibrosis.

The influence of human leukocyte antigen (HLA) mismatching on survival in adult and pediatric patients with cystic fibrosis (CF) after lung transplantation (LTx) is unknown. The United Network for Organ Sharing database was queried from 1987 to 2013 to determine the influence of HLA mismatching on survival in adult and pediatric CF LTx recipients by assessing the association of HLA mismatching with survival in first-time adult (aged ≥ 18 years) and pediatric (aged <18 years) recipients. Of 3149 adult and 489 pediatric patients with CF, 3145 and 489 were used for univariate Cox analysis, 2687 and 363 for Kaplan-Meier survival analysis, and 2073 and 257 for multivariate Cox analysis, respectively. Univariate analyses in adult and pediatric patients with CF demonstrated conflicting associations between HLA mismatching and survival (adult hazard ratio [HR], 1.0; 95% confidence interval [CI], 0.97-1.1; P = .45 vs pediatric HR, 0.87; 95% CI, 0.77-0.99; P = .032). Multivariate Cox models including both pediatric and adult patients confirmed that HLA mismatching had an initially protective effect at young ages (HR, 0.85; 95% CI, 0.73-0.99; P = .044) and that this protective effect diminished at older ages and was no longer associated with survival at P < .05 beyond age 10 years. HLA mismatching has significantly different implications for survival after LTx in adult compared with pediatric patients with CF.

Hayes D Jr ，Auletta JJ ，Whitson BA ，Black SM ，Kirkby S ，Tobias JD ，Mansour HM ... -  《-》

Influence of diabetes on survival in patients with cystic fibrosis before and after lung transplantation.

The influence of diabetes mellitus (DM) on survival in patients with cystic fibrosis (CF) before and after lung transplantation is not well studied. To determine the influence of DM in patients with CF, the United Network for Organ Sharing database (2005-2013) was queried for 2 cohorts: first-time lung transplant candidates who were not transplanted and first-time transplant recipients. A total of 679 patients with CF had data on DM status at listing and did not undergo transplantation. In this cohort, DM was associated with significant increase in mortality hazard as shown by an adjusted multivariate Cox model fitted to the whole cohort (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.1-1.8; P = .012) and by a Cox model stratified on pairs of DM and non-DM patients matched on the propensity of having DM at listing (HR, 1.9; 95% CI, 1.2-2.9; P = .003). In comparison, a total of 1464 patients with CF had data on DM status at listing and received a transplant, but DM at listing was not associated with posttransplant survival. The lack of association between DM and mortality hazard was evident in a multivariate Cox regression model fitted to the whole sample (HR, 1.0; 95% CI, 0.82-1.2; P = .98) and a Cox regression model stratified on matched pairs of DM and non-DM patients (HR, 1.1; 95% CI, 0.82-1.5; P = .56). The presence of DM is associated with significantly increased risk for death in patients with CF on the wait list before lung transplantation, but does not influence survival after transplantation.

Hayes D Jr ，Patel AV ，Black SM ，McCoy KS ，Kirkby S ，Tobias JD ，Mansour HM ，Whitson BA ... -  《-》

Influence of HLA Mismatching on Survival in Lung Transplantation.

Hayes D Jr ，Whitson BA ，Ghadiali SN ，Tobias JD ，Mansour HM ，Black SM ... -  《-》

Pulmonary Artery Pressure and Benefit of Lung Transplantation in Adult Cystic Fibrosis Patients.

The effect of lung transplantation (LTx) in patients afflicted with cystic fibrosis (CF) and pulmonary hypertension (PH) at placement on the waiting list is not well studied. To predict the relationship between initial mean pulmonary artery pressure (MPAP) and hazard ratio (HR) of death after listing associated with LTx in adult patients with CF, the United Network for Organ Sharing database was queried for the years 2005 to 2013. Survival was assessed from waiting list entry until death on the waiting list, death after LTx, or censoring. A multivariate Cox model was performed to estimate the HR of LTx conditional on MPAP at listing. Of 1,841 patients with CF, 10% (177) died on the waiting list, 18% (325) were censored without undergoing LTx, and 73% (1,339) underwent transplantation, 361 of whom died after transplantation. A multivariate Cox model of survival since list entry including 1,336 patients found a protective but statistically insignificant benefit of LTx for patients whose MPAP at listing was 25 mm Hg (HR, 0.879; 95% confidence interval [CI], 0.657-1.177; p = 0.388), yet LTx was predicted to be more protective at higher initial MPAP levels, as indicated by the significant interaction term between LTx and MPAP (HR, 0.953; 95% CI, 0.928-0.978; p < 0.001). The predicted LTx HR and 95% CI were protective (HR < 1) at p < 0.05 for patients with MPAP greater than or equal to 30 mm Hg at listing. Survival benefit of LTx in CF was increasingly protective at higher MPAP levels, with a severity level of PH established above which a survival advantage of LTx was found.

Hayes D Jr ，Tumin D ，Daniels CJ ，McCoy KS ，Mansour HM ，Tobias JD ，Kirkby SE ... -  《-》

Pretransplant Panel Reactive Antibodies and Lung Transplant Outcomes in Children.

Background Pre-lung transplant (LTx) panel reactive antibody (PRA) levels are associated with adverse outcomes in adult LTx recipients, but their impact in pediatric LTx recipients is unknown. Methods The United Network for Organ Sharing registry was queried from 2004 to 2013 to compare survival between pediatric LTx recipients with PRA class I and II levels = 0 versus > 0. Results Overall, 333 pediatric LTx recipients had data on class I or II PRA and were included in the analysis. Univariate analysis demonstrated that PRA > 0 was not associated with survival benefit for class I (hazard ratio [HR] = 0.985; 95% confidence interval [CI]: 0.623, 1.555; p = 0.947) or class II (HR = 1.080; 95% CI: 0.657, 1.774; p = 0.762) PRA. Multivariate Cox models confirmed no significant association with mortality hazard for both class I (HR = 1.230; 95% CI: 0.641, 2.363; p = 0.533) and class II (HR = 0.847; 95% CI: 0.359, 1.997; p = 0.704) PRA. Multivariate logistic regression models identified no association between class I or class II and acute rejection within 3 years of LTx. Conclusions Pretransplant class I and II PRA levels > 0 were not associated with mortality or acute rejection in pediatric LTx recipients.

Hayes D Jr ，Kopp BT ，Sheikh SI ，Shell RD ，Paul GR ，McConnell PI ，Tobias JD ，Tumin D ... -  《-》