Pacht Eric R, DeMichele Stephen J, Nelson Jeffrey L, Hart Judy, Wennberg Ann K, Gadek James E
Pulmonary and Critical Care Division, Ohio State University Medical Center, Columbus, USA.
Crit Care Med. 2003 Feb;31(2):491-500. doi: 10.1097/01.CCM.0000049952.96496.3E.
Previously, we showed that acute respiratory distress syndrome patients fed an enteral diet containing eicosapentaenoic acid and gamma-linolenic acid and elevated antioxidants (EPA+GLA; Oxepa) had significantly reduced pulmonary inflammation, increased oxygenation, and improved clinical outcomes. In a subset of acute respiratory distress syndrome patients from this trial, we performed a preliminary examination of the potential mechanisms underlying these clinical improvements by retrospectively testing the hypothesis that enteral feeding with EPA+GLA could reduce alveolar-capillary membrane protein permeability and the production of interleukin (IL)-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4 that are responsible, in part, for pulmonary inflammation.
Prospective, randomized, double-blind, controlled clinical trial.
Intensive Care Unit of the Ohio State University Medical Center.
A total of 67 patients were enrolled who met defined criteria for acute lung injury/acute respiratory distress syndrome.
A total of 43 of 67 evaluable patients randomly received either EPA+GLA or an isonitrogenous, isocaloric standard diet that was tube fed at a minimum caloric delivery of 75% of basal energy expenditure times 1.33 for at least 4 to 7 days.
Bronchoalveolar lavage (BAL) was performed at baseline and study days 4 and 7 to obtain BAL fluid (BALF) for measurement of total protein, ceruloplasmin, and transferrin, total neutrophil count, IL-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4. Oxygenation, measured as Pao2/Fio2, was assessed before BAL. Patients fed EPA+GLA had a significant reduction in BALF ceruloplasmin and IL-8 during the study as compared with patients fed the control diet. BALF levels of total protein, neutrophils, and leukotriene B4 tended to decrease in EPA+GLA patients over the course of the study as compared with control patients. BALF levels of IL-6 declined similarly during the study in both groups. A trend toward a reduction in BALF tumor necrosis factor-alpha was observed on study day 7 in the EPA+GLA group as compared with control patients. Significant improvements in oxygenation (Pao2/Fio2) occurred in EPA+GLA patients on study day 4 as compared with controls. Correlation analysis revealed significant relationships between BALF neutrophil counts and indices of alveolar-capillary membrane protein permeability, IL-8, and leukotriene B4.
This preliminary investigation showing a decrease in BALF levels of IL-8 and leukotriene B4 and the associated reduction of BALF neutrophils and alveolar membrane protein permeability in acute respiratory distress syndrome patients fed EPA+GLA support, in part, the potential mechanisms underlying the previously described clinical improvements with this diet. Additional controlled studies are needed to confirm these findings.
此前,我们发现,给急性呼吸窘迫综合征患者喂食含二十碳五烯酸和γ-亚麻酸且抗氧化剂含量较高的肠内饮食(EPA+GLA;奥克赛帕),可显著减轻肺部炎症、改善氧合并提高临床疗效。在该试验的一部分急性呼吸窘迫综合征患者中,我们通过回顾性检验肠内喂食EPA+GLA可降低肺泡-毛细血管膜蛋白通透性以及白细胞介素(IL)-8、IL-6、肿瘤坏死因子-α和白三烯B4的产生这一假设,对这些临床改善的潜在机制进行了初步研究,这些物质在一定程度上导致肺部炎症。
前瞻性、随机、双盲、对照临床试验。
俄亥俄州立大学医学中心重症监护病房。
共纳入67例符合急性肺损伤/急性呼吸窘迫综合征既定标准的患者。
67例可评估患者中的43例随机接受EPA+GLA或等氮、等热量的标准饮食,通过管饲法以至少基础能量消耗的75%乘以1.33的最低热量供给量喂食至少4至7天。
在基线以及研究第4天和第7天进行支气管肺泡灌洗(BAL),以获取支气管肺泡灌洗液(BALF),用于测量总蛋白、铜蓝蛋白、转铁蛋白、中性粒细胞总数、IL-8、IL-6、肿瘤坏死因子-α和白三烯B4。在进行BAL之前评估以Pao2/Fio2衡量的氧合情况。与喂食对照饮食的患者相比,喂食EPA+GLA的患者在研究期间BALF铜蓝蛋白和IL-8显著降低。与对照患者相比,在研究过程中,EPA+GLA组患者BALF中的总蛋白、中性粒细胞和白三烯B4水平有下降趋势。两组患者在研究期间BALF中IL-6水平的下降情况相似。与对照患者相比,在研究第7天,EPA+GLA组观察到BALF肿瘤坏死因子-α有下降趋势。与对照组相比,EPA+GLA组患者在研究第4天氧合(Pao2/Fio2)有显著改善。相关性分析显示,BALF中性粒细胞计数与肺泡-毛细血管膜蛋白通透性指标、IL-8和白三烯B4之间存在显著关系。
这项初步研究表明,喂食EPA+GLA的急性呼吸窘迫综合征患者BALF中IL-8和白三烯B4水平降低,同时BALF中性粒细胞和肺泡膜蛋白通透性相应降低,这在一定程度上支持了此前所述该饮食临床改善的潜在机制。需要更多对照研究来证实这些发现。