Section of Pulmonary and Critical Care Medicine, Department of Medicine, Yale University School of Medicine, 300 Cedar Street, PO Box 208057, New Haven, Connecticut 06520-8057, USA.
Eur J Endocrinol. 2012 Jan;166(1):121-9. doi: 10.1530/EJE-11-0778. Epub 2011 Oct 17.
IGF1 and its most abundant binding protein, IGF-binding protein 3 (IGFBP3), have been implicated in fibrotic lung diseases and persistent acute respiratory distress syndrome (ARDS) due to profibrogenic and antiapoptotic activity. Whether circulating levels of IGF1 and IGFBP3 are altered in ARDS and whether they predict progression of and survival from ARDS remains unknown. This study aims to characterize the circulating levels of IGF1 and IGFBP3 in patients at risk for ARDS in relation to i) development of ARDS and ii) mortality among ARDS cases.
In this case-cohort study, consecutive patients with risk factors for ARDS admitted to the intensive care unit were enrolled and followed prospectively for the development of ARDS. Cases were followed for all-cause mortality through day 60. Of the 2397 patients enrolled in the parent study, plasma samples were available in 531 (22%) patients (356 controls and 175 cases) from early in presentation. Total plasma IGF1 and IGFBP3 levels were measured.
After adjusting for relevant clinical covariates including severity of illness, IGF1 and IGFBP3 levels were significantly lower in ARDS cases than in controls (odds ratio (OR), 0.58; P=0.006; OR, 0.57; P=0.0015 respectively). Among the ARDS cases, IGF1 and IGFBP3 levels were significantly lower in the 78 (45%) non-survivors (hazard ratio (HR), 0.70; P=0.024; HR, 0.69; P=0.021 respectively).
Lower circulating levels of IGF1 and IGFBP3 were independently associated with ARDS case status. Furthermore, lower levels were associated with mortality among the ARDS cases. These data support the role of the IGF pathway in ARDS.
胰岛素样生长因子 1（IGF1）及其最丰富的结合蛋白，IGF 结合蛋白 3（IGFBP3），与纤维性肺疾病和持续性急性呼吸窘迫综合征（ARDS）有关，因为它们具有促纤维化和抗细胞凋亡的活性。ARDS 患者的循环 IGF1 和 IGFBP3 水平是否改变，以及它们是否预测 ARDS 的进展和存活仍然未知。本研究旨在描述 ARDS 高危患者的循环 IGF1 和 IGFBP3 水平与以下两方面的关系：i）ARDS 的发展和 ii）ARDS 病例的死亡率。
在这项病例队列研究中，连续入组因 ARDS 危险因素而入住重症监护病房的患者，并前瞻性随访其发生 ARDS 的情况。病例通过第 60 天的全因死亡率进行随访。在最初研究中，共有 2397 名患者入组，其中 531 名（22%）患者（356 名对照和 175 名病例）在入组时早期采集了血浆样本。测量了总血浆 IGF1 和 IGFBP3 水平。
在调整了包括疾病严重程度在内的相关临床协变量后，ARDS 病例的 IGF1 和 IGFBP3 水平明显低于对照组（比值比（OR），0.58；P=0.006；OR，0.57；P=0.0015）。在 ARDS 病例中，78 名（45%）非幸存者的 IGF1 和 IGFBP3 水平明显较低（风险比（HR），0.70；P=0.024；HR，0.69；P=0.021）。
较低的循环 IGF1 和 IGFBP3 水平与 ARDS 病例状态独立相关。此外，较低的水平与 ARDS 病例的死亡率相关。这些数据支持 IGF 通路在 ARDS 中的作用。
