Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:36

Article

Newton, Chad A.^1,2  Kozlitina, Julia¹  Lines, Jefferson R.¹  Kaza, Vaidehi²  Torres, Fernando²  Garcia, Christine Kim^1,2 

[1] Univ Texas Southwestern Med Ctr Dallas, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA

[2] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Div Pulm & Crit Care Med, Dallas, TX 75390 USA

关键词: lung transplant;    interstitial lung disease;    telomeres;    telomere length;    primary graft dysfunction;    chronic lung allograft;    dysfunction;    survival;   

DOI  :  10.1016/j.healun.2017.02.005

来源: Elsevier

【 摘 要 】

BACKGROUND: Prior studies have shown that patients with pulmonary fibrosis with mutations in the telomerase genes have a high rate of certain complications after lung transplantation. However, few studies have investigated clinical outcomes based on leukocyte telomere length. METHODS: We conducted an observational cohort study of all patients with pulmonary fibrosis who underwent lung transplantation at a single center between January 1, 2007, and December 31, 2014. Leukocyte telomere length was measured from a blood sample collected before lung transplantation, and subjects were stratified into 2 groups (telomere length <10th percentile vs >= 10th percentile). Primary outcome was post lung transplant survival. Secondary outcomes included incidence of allograft dysfunction, non-pulmonary organ dysfunction, and infection. RESULTS: Approximately 32% of subjects had a telomere length <10th percentile. Telomere length <10th percentile was independently associated with worse. survival (hazard ratio 10.9, 95% confidence interval 2.7-44.8, p = 0.001). Telomere length <10th percentile was also independently associated with a shorter time to onset of chronic lung allograft dysfunction (hazard ratio 6.3, 95% confidence interval 2.0-20.0, p = 0.002). Grade 3 primary graft dysfunction occurred more frequently in the <10th percentile group compared with the >= 10th percentile group (28% vs 7%; p = 0.034). There was no difference between the 2 groups in incidence of acute cellular rejection, cytopenias, infection, or renal dysfunction. CONCLUSIONS: Telomere length <10th percentile was associated with worse survival and shorter time to onset of chronic lung allograft dysfunction and thus represents a biomarker that may aid in risk stratification of patients with pulmonary fibrosis before lung transplantation. (C) 2017 International Society for Heart and Lung Transplantation. All rights reserved.

【 授权许可】

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