Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2020 Jan 16;55(1):1901044.
doi: 10.1183/13993003.01044-2019. Print 2020 Jan.

Peripheral blood leukocyte telomere length is associated with survival of sepsis patients

Shuo Liu  1   2   3 , Chunxue Wang  4 , Gary Green  1 , Hanjing Zhuo  1 , Kathleen D Liu  5 , Kirsten N Kangelaris  6 , Antonio Gomez  1 , Alejandra Jauregui  1 , Kathryn Vessel  7 , Serena Ke  1 , Carolyn Hendrickson  1 , Michael A Matthay  1 , Carolyn S Calfee  1 , Lorraine B Ware  4 , Paul J Wolters  8
Affiliations
Observational Study

Peripheral blood leukocyte telomere length is associated with survival of sepsis patients

Shuo Liu et al. Eur Respir J. .

Abstract

Shorter peripheral blood leukocyte (PBL) telomere length (TL) has been associated with poor outcomes in various chronic lung diseases. Whether PBL-TL is associated with survival from critical illness was tested in this study.We analysed data from a prospective observational cohort study of 937 critically ill patients at Vanderbilt University Medical Center (VUMC). PBL-TL was measured using quantitative PCR of DNA isolated from PBLs. Findings were validated in an independent cohort of 394 critically ill patients with sepsis admitted to the University of California San Francisco (UCSF).In the VUMC cohort, shorter PBL-TL was associated with worse 90-day survival (adjusted hazard ratio (aHR) 1.3, 95% CI 1.1-1.6 per 1 kb TL decrease; p=0.004); in subgroup analyses, shorter PBL-TL was associated with worse 90-day survival for patients with sepsis (aHR 1.5, 95% CI 1.2-2.0 per 1 kb TL decrease; p=0.001), but not trauma. Although not associated with development of acute respiratory distress syndrome (ARDS), among ARDS subjects, shorter PBL-TL was associated with more severe ARDS (OR 1.7, 95% CI 1.2-2.5 per 1 kb TL decrease; p=0.006). The associations of PBL-TL with survival (adjusted HR 1.6, 95% CI 1.2-2.1 per 1 kb TL decrease; p=0.003) and risk for developing severe ARDS (OR 2.5, 95% CI 1.1-6.3 per 1 kb TL decrease; p=0.044) were validated in the UCSF cohort.Short PBL-TL is strongly associated with worse survival and more severe ARDS in critically ill patients, especially patients with sepsis. These findings suggest that telomere dysfunction may contribute to outcomes from critical illness.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: S. Liu reports grants from National Natural Science Foundation of China, during the conduct of the study. Conflict of interest: C. Wang has nothing to disclose. Conflict of interest: G. Green has nothing to disclose. Conflict of interest: H. Zhuo has nothing to disclose. Conflict of interest: K.D. Liu has nothing to disclose. Conflict of interest: K.N. Kangelaris has nothing to disclose. Conflict of interest: A. Gomez has nothing to disclose. Conflict of interest: A. Jauregui has nothing to disclose. Conflict of interest: K. Vessel has nothing to disclose. Conflict of interest: S. Ke has nothing to disclose. Conflict of interest: C. Hendrickson has nothing to disclose. Conflict of interest: M.A. Matthay reports grants from NIH/NHLBI (for research and clinical trials of ARDS and sepsis), Department of Defense (to carry out a clinical trial of ARDS) and Bayer Pharmaceuticals (for an observational research study of ARDS), and personal fees from Cerus Therapeutics (ARDS consultation) and CSL Behring (ARDS consultation), outside the submitted work. Conflict of interest: C.S. Calfee reports grants from NIH, during the conduct of the study; grants from GlaxoSmithKline (for an observational study of sepsis and ARDS), grants and personal fees from Bayer (for an observational study of ARDS and consultancy about ARDS), and personal fees from Prometic (consultancy), CSL Behring (medical advisory board), Roche/Genentech (consultancy) and Quark (consultancy), outside the submitted work. Conflict of interest: L.B. Ware reports grants from National Institutes of Health, during the conduct of the study; personal fees from Quark Pharmaceuticals (advisory board), CSL Behring (advisory board) and Bayer (advisory board), outside the submitted work. Conflict of interest: P.J. Wolters reports grants from MedImmune, Genentech and Boehringer Ingelheim, and personal fees from Roche, Boehringer Ingelheim, Blade Therapeutics and Pliant, outside the submitted work.

Figures

FIGURE 1
FIGURE 1
Shorter telomere lengths are associated with worse survival for critically ill patients in the Vanderbilt University Medical Center (VUMC) cohort, VUMC sepsis subgroup and University of California San Francisco (UCSF) sepsis cohort. a) VUMC cohort (n=937); b) VUMC sepsis subgroup (n=368); c) UCSF sepsis cohort (n=394). Estimated survival for critically ill patients stratified by telomere length (TL) quartiles for survival. Q4: longest quartile; Q3: 50–75%; Q2: 25–50%; Q1: shortest quartile.
FIGURE 2
FIGURE 2
Relationship between peripheral blood leukocyte telomere lengths and mortality for critically ill patients in a logistic regression model. a) Vanderbilt University Medical Center (VUMC) cohort; b) VUMC sepsis subgroup; c) University of California San Francisco sepsis cohort. Model controlled for age, male sex, ethnicity, smoking status and Acute Physiology and Chronic Health Evaluation (APACHE) II score.
See this image and copyright information in PMC

Comment in

References

    1. McClave SA, Taylor BE, Martindale RG, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016; 40: 159–211. - PubMed
    1. Fan E, Zakhary B, Amaral A, et al. Liberation from mechanical ventilation in critically ill adults. An official ATS/ACCP clinical practice guideline. Ann Am Thorac Soc 2017; 14: 441–443. - PubMed
    1. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med 2013; 369: 840–851. - PubMed
    1. Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis 2013; 13: 260–268. - PMC - PubMed
    1. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000; 342: 1334–1349. - PubMed

Publication types