PT  - JOURNAL ARTICLE
AU  - Shuo Liu
AU  - Chunxue Wang
AU  - Gary Green
AU  - Hanjing Zhuo
AU  - Kathleen D. Liu
AU  - Kirsten N. Kangelaris
AU  - Antonio Gomez
AU  - Alejandra Jauregui
AU  - Kathryn Vessel
AU  - Serena Ke
AU  - Carolyn Hendrickson
AU  - Michael A. Matthay
AU  - Carolyn S. Calfee
AU  - Lorraine B. Ware
AU  - Paul J. Wolters
TI  - Peripheral Blood Leukocyte Telomere Length is Associated with Survival of Sepsis Patients
AID  - 10.1183/13993003.01044-2019
DP  - 2019 Jan 01
TA  - European Respiratory Journal
PG  - 1901044
4099  - http://erj.ersjournals.com/content/early/2019/09/25/13993003.01044-2019.short
4100  - http://erj.ersjournals.com/content/early/2019/09/25/13993003.01044-2019.full
AB  - 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). TL was measured by qPCR of DNA isolated from PBL. 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 HR 1.3 per 1 kb TL decrease, 95%CI [1.1–1.6], p=0.004); in subgroup analyses, shorter PBL-TL was associated with worse 90-day survival for patients with sepsis (adjusted HR 1.5 per 1 kb TL decrease, 95%CI [1.2–2.0], p=0.001) but not trauma. Although not associated with development of ARDS, among ARDS subjects, shorter PBL-TL was associated with more severe ARDS (OR 1.7 per 1 kb TL decrease, 95%CI [1.2–2.5], p=0.006). The associations of PBL-TL with survival (adjusted HR 1.6 per 1 kb TL decrease, 95%CI [1.2–2.1], p=0.003) and risk for developing severe ARDS (OR 2.5 per 1 kb TL decrease, 95%CI [1.1–6.3], p-value=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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Liu reports grants from National Natural Science Foundation of China, during the conduct of the studyConflict of interest: Dr. Wang has nothing to disclose.Conflict of interest: Dr. Green has nothing to disclose.Conflict of interest: Dr. Zhuo has nothing to disclose.Conflict of interest: Dr. Liu has nothing to disclose.Conflict of interest: Dr. Kangelaris has nothing to disclose.Conflict of interest: Dr. Gomez has nothing to disclose.Conflict of interest: Dr. Jauregui has nothing to discloseConflict of interest: Kathryn Vessel has nothing to discloseConflict of interest: Serena Ke has nothing to disclose.Conflict of interest: Dr. Hendrickson has nothing to disclose.Conflict of interest: Dr. Matthay reports grants from NIH/NHLBI, grants from Department of Defense, grants from Bayer Pharmaceuticals, personal fees from Cerus Therapeutics, personal fees from CSL Behring, outside the submitted work.Conflict of interest: Dr. Calfee reports grants from NIH, during the conduct of the study; grants from GlaxoSmithKline, grants and personal fees from Bayer, personal fees from Prometic, personal fees from CSL Behring, personal fees from Roche/Genentech, personal fees from Quark, outside the submitted work.Conflict of interest: Dr. Ware reports grants from National Institutes of Health, during the conduct of the study; personal fees from Quark Pharmaceuticals, personal fees from CSL Behring, personal fees from Bayer, outside the submitted work.Conflict of interest: Dr. Wolters reports grants from medimmune, grants from Genentech, personal fees from Roche, personal fees from Boehringer Ingelheim, personal fees from Blade Therapeutics, grants from Boehringer Ingelheim, personal fees from Pliant, outside the submitted work.