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.
Abstract
Shorter peripheral blood leukocyte telomere length is strongly associated with worse survival and more severe ARDS in critically ill patients with sepsis http://bit.ly/2mWHKxf
Footnotes
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Author contributions: P.J. Wolters, C.S. Calfee, L.B. Ware and M.A. Matthay designed the study. S. Liu and G. Green performed telomere length measurements. C. Wang and S. Liu analysed the data. H. Zhuo, L.B. Ware, C.S. Calfee, M.A. Matthay, K.D. Liu, K.N. Kangelaris, A. Gomez, A. Jauregui, K. Vessel, S. Ke and C. Hendrickson collected data for the study. S. Liu drafted the manuscript. All authors contributed to study conduct, data interpretation and manuscript preparation.
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.
Support statement: The study was funded in part by NIH grants HL103836 and HL135849 (L.B. Ware), HL131621 and HL140026 (C.S. Calfee), HL51856 (M.A. Matthay), National Natural Science Foundation of China 81700063 (S. Liu), and the Nina Ireland Program for Lung Health. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received May 25, 2019.
- Accepted September 21, 2019.
- Copyright ©ERS 2020
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