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-to-moderate 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; I² = 20.4% and adjusted HR = 2.49, 95%CI:1.74-3.57; I² = 46.2%) and ascending chronological year of LTx (N = 4207, unadjusted HR = 0.98, 95%CI:0.97-0.98, I² = 4.8%) were predictors of post-LTx mortality. Male gender (N = 2903, adjusted HR = 1.12, 95%CI:1.0-1.26, I² = 0%) and age in adults (N = 3677, unadjusted HR = 0.99, 95%CI:0.97-1.00; I² = 64.1% and N = 2605, adjusted HR = 0.98, 95%CI:0.97-0.99; I² = 34.3%) had borderline significant associations with post-LTx mortality. P. aeruginosa colonization, forced expiratory volume in one second (FEV₁), 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 FEV₁, 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.

Keywords: Cystic fibrosis; Lung transplantation; Mortality; Predictors.