PMID- 31619475 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210917 IS - 1399-3003 (Electronic) IS - 0903-1936 (Print) IS - 0903-1936 (Linking) VI - 55 IP - 1 DP - 2020 Jan TI - Peripheral blood leukocyte telomere length is associated with survival of sepsis patients. LID - 10.1183/13993003.01044-2019 [doi] LID - 1901044 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). 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. CI - Copyright (c)ERS 2020. FAU - Liu, Shuo AU - Liu S AUID- ORCID: 0000-0002-4067-2261 AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. AD - Dept of Respiratory Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China. AD - Dept of Respiratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China. FAU - Wang, Chunxue AU - Wang C AD - Dept of Medicine and Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA. FAU - Green, Gary AU - Green G AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Zhuo, Hanjing AU - Zhuo H AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Liu, Kathleen D AU - Liu KD AD - Division of Nephrology, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Kangelaris, Kirsten N AU - Kangelaris KN AD - Division of Hospital Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Gomez, Antonio AU - Gomez A AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Jauregui, Alejandra AU - Jauregui A AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Vessel, Kathryn AU - Vessel K AD - The Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA. FAU - Ke, Serena AU - Ke S AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Hendrickson, Carolyn AU - Hendrickson C AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Matthay, Michael A AU - Matthay MA AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Calfee, Carolyn S AU - Calfee CS AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA. FAU - Ware, Lorraine B AU - Ware LB AD - Dept of Medicine and Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA. FAU - Wolters, Paul J AU - Wolters PJ AD - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, San Francisco, CA, USA paul.wolters@ucsf.edu. LA - eng GR - R01 HL135849/HL/NHLBI NIH HHS/United States GR - R35 HL140026/HL/NHLBI NIH HHS/United States GR - R01 HL051856/HL/NHLBI NIH HHS/United States GR - R01 HL131621/HL/NHLBI NIH HHS/United States GR - K23 HL133495/HL/NHLBI NIH HHS/United States GR - R37 HL051856/HL/NHLBI NIH HHS/United States GR - R01 HL139897/HL/NHLBI NIH HHS/United States GR - K24 HL103836/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Observational Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200116 PL - England TA - Eur Respir J JT - The European respiratory journal JID - 8803460 SB - IM CIN - Eur Respir J. 2020 Jan 16;55(1):. PMID: 31949102 MH - Cohort Studies MH - Humans MH - Leukocytes MH - Prospective Studies MH - *Sepsis/genetics MH - *Telomere PMC - PMC7359873 MID - NIHMS1604640 COIS- 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. EDAT- 2019/10/18 06:00 MHDA- 2021/06/22 06:00 PMCR- 2021/01/16 CRDT- 2019/10/18 06:00 PHST- 2019/05/25 00:00 [received] PHST- 2019/09/21 00:00 [accepted] PHST- 2019/10/18 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2019/10/18 06:00 [entrez] PHST- 2021/01/16 00:00 [pmc-release] AID - 13993003.01044-2019 [pii] AID - 10.1183/13993003.01044-2019 [doi] PST - epublish SO - Eur Respir J. 2020 Jan 16;55(1):1901044. doi: 10.1183/13993003.01044-2019. Print 2020 Jan.