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

J Heart Lung Transplant. 2017 Aug;36(8):845-853. doi: 10.1016/j.healun.2017.02.005. Epub 2017 Feb 4.

Abstract

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.

Keywords: chronic lung allograft dysfunction; interstitial lung disease; lung transplant; primary graft dysfunction; survival; telomere length; telomeres.

Publication types

  • Observational Study

MeSH terms

  • Chronic Disease
  • DNA / genetics
  • Female
  • Follow-Up Studies
  • Graft Survival*
  • Humans
  • Incidence
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Postoperative Complications*
  • Postoperative Period
  • 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
  • Survival Rate / trends
  • Telomere / genetics*
  • Telomere Homeostasis / genetics*
  • Texas / epidemiology

Substances

  • DNA