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

• Published in: The Journal of heart and lung transplantation Vol. 36; no. 8; pp. 845 - 853
• Main Authors: Newton, Chad A., Kozlitina, Julia, Lines, Jefferson R., Kaza, Vaidehi, Torres, Fernando, Garcia, Christine Kim
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2017
• Subjects: Chronic Disease; chronic lung allograft dysfunction; DNA - genetics; Female; Follow-Up Studies; Graft Survival; Humans; Incidence; interstitial lung disease; lung transplant; Lung Transplantation; Male; Middle Aged; Polymerase Chain Reaction; Postoperative Complications; Postoperative Period; primary graft dysfunction; Primary Graft Dysfunction - complications; Primary Graft Dysfunction - epidemiology; Primary Graft Dysfunction - genetics; Prospective Studies; Pulmonary Fibrosis - epidemiology; Pulmonary Fibrosis - etiology; Pulmonary Fibrosis - genetics; Risk Factors; Surgery; survival; Survival Rate - trends; Telomere - genetics; Telomere Homeostasis - genetics; telomere length; telomeres; Texas - epidemiology; chronic lung allograft dysfunction; lung transplant; interstitial lung disease; telomeres; survival; telomere length; primary graft dysfunction
• ISSN: 1053-2498; 1557-3117; 1557-3117
• DOI: 10.1016/j.healun.2017.02.005

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. 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. 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. 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.