Mortality Risk and Pulmonary Function in Adults With Cystic Fibrosis at Time of Wait Listing for Lung Transplantation.

Lung transplantation (LTx) benefit for survival in cystic fibrosis (CF) patients placed on the wait list is not well studied. To predict the relationship between initial forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and the hazard ratio (HR) associated with LTx in CF patients, the United Network for Organ Sharing database was queried from 2005 to 2006 for adult patients with CF. Survival was assessed from wait list entry time until death on wait list, death after LTx, or censoring. Multivariate Cox proportional hazards models were used to assess the effect of LTx. The first model estimated the HR of LTx with adjustment for FEV1 or FVC and other covariates, and the second model estimated the HR of LTx conditional on FEV1 or FVC at listing. Two hundred seventy-eight patients with CF were included in the cohort, and 277 were used for survival analysis. Lung transplantation reduced the risk for death controlling for FEV1 (HR, 0.601; 95% confidence interval, 0.375 to 0.964; p = 0.035) or controlling for FVC (HR, 0.547; 95% confidence interval, 0.336 to 0.889; p = 0.015). Interaction models found that the HR of LTx varied significantly across initial FEV1 and FVC, with the predicted LTx HR and 95% confidence interval being protective (HR < 1) at FEV1 of 25% or less and FVC of 40% or less, respectively. The benefit of LTx in adults with CF was significant at a lower baseline FEV1 than expected. A threshold for baseline FVC was established below which LTx was protective.

Hayes D Jr ，Kirkby S ，Whitson BA ，Black SM ，Sheikh SI ，Tobias JD ，Mansour HM ，Kopp BT ... -  《-》

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 ... -  《-》

Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation.

Hayes D Jr ，Kopp BT ，Tobias JD ，Woodley FW ，Mansour HM ，Tumin D ，Kirkby SE ... -  《-》

Heterogeneity in Survival in Adult Patients With Cystic Fibrosis With FEV(1) < 30% of Predicted in the United States.

Lung transplantation (LTx) is frequently considered for patients with cystic fibrosis (CF) when the FEV1 reaches < 30%. This study estimated transplant-free survival for patients with CF and an FEV1 < 30% and identified predictors of death without LTx. We conducted a retrospective cohort study using the CF Foundation Patient Registry from January 1, 2003 to December 31, 2013. Adult patients (≥ 18 years) with FEV1 < 30% prior to LTx were included. We performed Kaplan-Meier survival estimates censored at LTx. Multivariable Cox proportional hazard regression identified predictors of mortality. There were 3,340 patients with an FEV1 < 30%. Death without LTx occurred in 1,250 patients (37.4%); 951 patients (28.5%) underwent LTx; 918 patients (27.5%) remained alive without LTx at the end of follow-up; and 221 patients (6.6%) were lost to follow-up. Median transplant-free survival after FEV1 < 30% was 6.6 years (95% CI, 5.9-7.0). Adjusted predictors of death without LTx included supplemental oxygen use (hazard ratio [HR], 2.1; 95% CI, 1.7-2.6), Burkholderia cepacia infection (HR, 1.8; 95% CI, 1.3-2.6), BMI ≤ 18 (HR, 1.6; 95% CI, 1.3-1.9), female sex (HR, 1.6; 95% CI, 1.2-2.0), CF-related diabetes in patients receiving insulin (HR, 1.4; 95% CI, 1.2-1.8), and ≥ one exacerbation per year (HR, 1.7; 95% CI, 1.3-2.2 vs. 0 exacerbations). Median survival was > 6.5 years for patients with CF and an FEV1 < 30%, exceeding prior survival estimates. There was substantial heterogeneity in survival, with some patients with CF dying soon after reaching this lung function threshold and others living for many years. For this reason, we conclude that FEV1 < 30% remains an important marker of disease severity for patients with CF. Patients with a supplemental oxygen requirement or frequent exacerbations should have prompt referral because of their increased risk of death.

Ramos KJ ，Quon BS ，Heltshe SL ，Mayer-Hamblett N ，Lease ED ，Aitken ML ，Weiss NS ，Goss CH ... -  《-》

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 ... -  《-》