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. 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

中文翻译：

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外周血白细胞端粒长度与脓毒症患者的存活率相关

较短的外周血白细胞 (PBL) 端粒长度 (TL) 与各种慢性肺病的不良预后有关。本研究检验了 PBL-TL 是否与危重疾病的存活率相关。我们分析了范德比尔特大学医学中心 (VUMC) 对 937 名危重患者的前瞻性观察队列研究的数据。使用从 PBL 中分离的 DNA 的定量 PCR 测量 PBL-TL。结果在一个由 394 名被加州大学旧金山分校 (UCSF) 录取的重症脓毒症患者组成的独立队列中得到验证。在 VUMC 队列中，较短的 PBL-TL 与较差的 90 天生存率相关（调整后的风险比 (aHR) 1.3，95% CI 1.1–1.6 每 1 kb TL 减少；p=0.004）；在亚组分析中，对于脓毒症患者，较短的 PBL-TL 与较差的 90 天存活率相关（aHR 1.5，95% CI 1.2–2.0 每 1 kb TL 减少；p=0.001），但与创伤无关。尽管与急性呼吸窘迫综合征 (ARDS) 的发展无关，但在 ARDS 受试者中，较短的 PBL-TL 与更严重的 ARDS 相关（OR 1.7，95% CI 1.2–2.5 每 1 kb TL 减少；p=0.006）。PBL-TL 与生存率（调整后的 HR 1.6，95% CI 1.2–2.1 每 1 kb TL 减少；p=0.003）和发生严重 ARDS 的风险（OR 2.5，95% CI 1.1–6.3 每 1 kb TL 减少）的关联; p=0.044) 在 UCSF 队列中得到验证。短 PBL-TL 与危重患者，尤其是败血症患者的较差生存率和更严重的 ARDS 密切相关。这些发现表明端粒功能障碍可能导致危重疾病的结果。