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

Chad A. Newton, Julia Kozlitina, Jefferson R. Lines, Vaidehi Kaza, Fernando Torres, Christine Kim Garcia

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22 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of Heart and Lung Transplantation
DOIs
StateAccepted/In press - 2017

Fingerprint

Lung Transplantation
Pulmonary Fibrosis
Telomere
Allografts
Lung
Survival
Primary Graft Dysfunction
Leukocytes
Confidence Intervals
Telomerase
Incidence
Infection
Observational Studies
Cohort Studies
Biomarkers
Transplants
Kidney
Mutation
Genes

Keywords

  • Chronic lung allograft dysfunction
  • Interstitial lung disease
  • Lung transplant
  • Primary graft dysfunction
  • Survival
  • Telomere length
  • Telomeres

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

@article{a241924c0b694951bc57023b203dc61f,
title = "Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival",
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",
author = "Newton, {Chad A.} and Julia Kozlitina and Lines, {Jefferson R.} and Vaidehi Kaza and Fernando Torres and Garcia, {Christine Kim}",
year = "2017",
doi = "10.1016/j.healun.2017.02.005",
language = "English (US)",
journal = "Journal of Heart and Lung Transplantation",
issn = "1053-2498",
publisher = "Elsevier USA",

}

TY - JOUR

T1 - Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival

AU - Newton, Chad A.

AU - Kozlitina, Julia

AU - Lines, Jefferson R.

AU - Kaza, Vaidehi

AU - Torres, Fernando

AU - Garcia, Christine Kim

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Chronic lung allograft dysfunction

KW - Interstitial lung disease

KW - Lung transplant

KW - Primary graft dysfunction

KW - Survival

KW - Telomere length

KW - Telomeres

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U2 - 10.1016/j.healun.2017.02.005

DO - 10.1016/j.healun.2017.02.005

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C2 - 28262440

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JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

SN - 1053-2498

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