Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Vermont College of Medicine, HSRF 222, Burlington, VT 05405, USA.
Chest. 2010 Sep;138(3):568-77. doi: 10.1378/chest.10-0014. Epub 2010 Apr 30.
Obesity is associated with poor outcomes in many diseases, although recent data suggest that acute lung injury (ALI) is an exception. This is particularly interesting because obesity is marked by increased levels of proinflammatory mediators associated with increased morbidity and mortality in ALI. We hypothesized that cytokine response might be attenuated in patients who are obese and critically ill or that obesity might modify the relationship between plasma cytokines and clinical outcomes in ALI.
We analyzed plasma biomarker levels (interleukin [IL]-6, IL-8, tumor necrosis factor-alpha receptor 1, surfactant protein D [SP-D], soluble intracellular adhesion molecule, von Willebrand factor (vWF), protein C, and plasminogen activator inhibitor-1) collected at baseline and day 3 in 1,409 participants in prior National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network (ARDSNet) trials. BMI was calculated for each patient, and associations with cytokine levels and ventilator-free days (VFDs), organ failure-free days (OFDs), and mortality were investigated in regression models adjusting for confounders.
In adjusted analyses, plasma IL-6 (P = .052), IL-8 (P = .001), and SP-D (P < .001) were inversely related to BMI, whereas vWF (P = .001) and WBC count (P = .042) increased proportionally with BMI. BMI was not associated with increased morbidity or mortality and did not modify the association between baseline biomarker levels and mortality, VFDs, or OFDs.
Patients who are obese and have ALI have lower levels of several proinflammatory cytokines, suggesting that the inflammatory response may be altered in patients with ALI and a high BMI. Lower SP-D but higher vWF suggests decreased epithelial and increased endothelial injury in the lung of patients who are obese. Mechanisms by which obesity may modulate innate immunity in critical illness are unclear, and future studies should elucidate such mechanisms.
肥胖与许多疾病的不良预后相关，尽管最近的数据表明急性肺损伤（ALI）是一个例外。这一点尤其有趣，因为肥胖与ALI 发病率和死亡率增加相关的促炎介质水平升高有关。我们假设，在肥胖且患有危重病的患者中，细胞因子反应可能会减弱，或者肥胖可能会改变 ALI 患者血浆细胞因子与临床结局之间的关系。
我们分析了既往国家心肺血液研究所急性呼吸窘迫综合征网络（ARDSNet）试验中 1409 名参与者基线和第 3 天采集的血浆生物标志物水平（白细胞介素[IL]-6、IL-8、肿瘤坏死因子-α受体 1、表面活性蛋白 D [SP-D]、可溶性细胞间黏附分子、血管性血友病因子[vWF]、蛋白 C 和纤溶酶原激活物抑制剂-1）。为每个患者计算 BMI，并在调整混杂因素的回归模型中研究了 BMI 与细胞因子水平以及无呼吸机天数（VFDs）、无器官衰竭天数（OFDs）和死亡率之间的关系。
在调整后的分析中，血浆 IL-6（P =.052）、IL-8（P =.001）和 SP-D（P <.001）与 BMI 呈负相关，而 vWF（P =.001）和白细胞计数（P =.042）与 BMI 呈正相关。BMI 与发病率或死亡率的增加无关，也不会改变基线生物标志物水平与死亡率、VFDs 或 OFDs 之间的关联。
患有 ALI 的肥胖患者几种促炎细胞因子水平较低，表明肥胖的 ALI 患者的炎症反应可能发生改变。较低的 SP-D 但较高的 vWF 表明肥胖患者肺中的上皮细胞损伤减少而内皮细胞损伤增加。肥胖可能调节危重病中固有免疫的机制尚不清楚，未来的研究应该阐明这些机制。
