Pre-transplant factors associated with mortality after lung transplantation in cystic fibrosis: A systematic review and meta-analysis

Abstract

Background: Mortality risk stratification is essential in lung transplantation (LTx) to allow listing, prioritization and mitigating strategies. In cystic fibrosis (CF) patients, predictors of post-LTx mortality are not established. Methods: For this systematic review and meta-analysis, seven databases were searched until January 3, 2018 to identify predictors of post-LTx mortality in CF. We excluded studies of multi-organ transplantation, re-transplantation and graft survival. For multiple studies assessing the same population during overlapping time-periods, the largest one was analyzed. Risk of bias was assessed with the Newcastle-Ottawa scale (NOS). Pooled hazard ratios were calculated using random-effects models. Results: Fifty-four studies were included in the systematic review and 11 studies in the meta-analyses (low-tomoderate bias risk, NOS score ≥ 5). Among 10 factors assessed in the meta-analysis, B. cepacia complex (BCC) (N = 1451, unadjusted HR = 2.35, 95%CI:1.80-3.06; I 2 = 20.4% and adjusted HR = 2.49, 95%CI:1.74-3.57; I 2 = 46.2%) and ascending chronological year of LTx (N = 4207, unadjusted HR = 0.98, 95%CI:0.97-0.98, I 2 = 4.8%) were predictors of post-LTx mortality. Male gender (N = 2903, adjusted HR = 1.12, 95%CI:1.0-1.26, I 2 = 0%) and age in adults (N = 3677, unadjusted HR = 0.99, 95%CI:0.97-1.00; I 2 = 64.1% and N = 2605, adjusted HR = 0.98, 95%CI:0.97-0.99; I 2 = 34.3%) had borderline significant associations with post-LTx mortality. P. aeruginosa colonization, forced expiratory volume in one second (FEV 1 ), pulmonary hypertension, body mass index (BMI), pancreatic insufficiency and CF-related diabetes (CFRD) were not predictors of mortality. Conclusions: BCC was associated with a higher post-LTx mortality whereas FEV 1 , pulmonary hypertension, BMI, CFRD and female gender were not associated with post-LTx mortality. These findings indicate that CF-specific risk estimates of post-LTx mortality should be considered.

Cystic fibrosis‐related diabetes before lung transplantation is associated with lower survival but does not affect long‐term renal function

“…It is worth noting that vancomycin, used to treat methicillin‐resistant Staphylococcus aureus (MRSA), is an additional nephrotoxic agent especially when combined to aminoglycoside, as well as additional agents, that is, antifungals. The microbiological status about MRSA and the use of other agents than aminoglycosides were not collected for this study because their use is very infrequent in our center; further works concerning the deleterious impact of MRSA need to be considered even though it does not appear as a studied predictor of posttransplant mortality in a recent meta‐analysis …”

Pancreatitis in Solid Organ Transplant Patients: A Review of the Literature

“…A systematic review by Koutsokera et al, including 54 studies, sought to identify pre-transplant factors that were associated with mortality after lung transplantation in patients with cystic fibrosis. They found that there was no difference in mortality after lung transplantation between the patients with pancreatic insufficiency and those without pancreatic insufficiency [20].…”

Organ Transplantation for Cystic Fibrosis

“…81 A BMI less than 18.5 has been associated with increased mortality both while awaiting lung transplantation and also post-lung transplant. 82 In contrast, a meta-analysis analyzing risk factors for posttransplant mortality did not find that malnutrition was associated with an increased risk of death, 83 and a recent registry review demonstrated that even in patients with CF and a BMI <17, survival was comparable to recipients with pulmonary fibrosis, 84 suggesting that mild malnutrition in itself should not preclude lung transplant referral and listing. The variable practices toward malnutrition and lung transplant candidacy and outcomes may be due to transplant-center experience and to the fact that the majority of patients gain weight following lung transplantation.…”

“…93 However, a recent meta-analysis showed that CFRD was not a predictor of mortality in patients with CF that undergo lung transplantation. 83 Glycemic control has been utilized as a surrogate for compliance during the evaluation process for lung transplantation and aggressive treatment of diabetes is recommended both prior to and following lung transplantation.…”