From the Department of Anesthesia, Intensive Care Medicine, and Pain Therapy, University Hospital Knappschaftskrankenhaus Bochum, Bochum, Germany (T.R., K.R., M.A.) Department of Anesthesia and Intensive Care Medicine, University Duisburg-Essen and University Hospital Essen, Essen, Germany (J.P., M.A.).
Anesthesiology. 2019 Mar;130(3):404-413. doi: 10.1097/ALN.0000000000002560.
WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Acute respiratory distress syndrome is defined according to clinical criteria, but lack of precise characterization may contribute to negative trials and impede personalized care. Polymorphisms of aquaporin-5, a key mediator of inflammation, may impact outcome. WHAT THIS ARTICLE TELLS US THAT IS NEW: In acute respiratory distress syndrome attributable to bacterial pneumonia, the C-allele of the aquaporin-5 -1364A/C promoter polymorphism is associated with less pulmonary inflammation and greater survival. This may improve characterization of acute respiratory distress syndrome and ultimately facilitate individualized care. BACKGROUND: The aquaporin-5 (AQP5) -1364A/C promoter single-nucleotide polymorphism is associated with an altered AQP5 expression and mortality in sepsis. Because AQP5 expression alters neutrophil cell migration, it could affect pulmonary inflammation and survival in bacterially evoked acute respiratory distress syndrome. Accordingly, the authors tested the hypotheses that the AC/CC genotype in patients with bacterially evoked pneumonia resulting in acute respiratory distress syndrome is associated with (1) attenuated pulmonary inflammation and (2) higher 30-day survival. METHODS: In this prospective, observational study, bronchoalveolar lavage and blood sampling were performed within 24 h of intensive care unit admission. In 136 Caucasian patients with bacterially evoked acute respiratory distress syndrome, genotype of the AQP5 -1364A/C promoter polymorphism, bronchoalveolar lavage total protein, albumin, white cell concentrations, and lactate dehydrogenase activity were measured to evaluate the relationship between genotypes and survival. RESULTS: AC/CC patients as well as survivors showed lower bronchoalveolar lavage protein (0.9 mg/ml vs. 2.3 mg/ml, P < 0.001 and 1.6 mg/ml vs. 2.6 mg/ml, P = 0.035), albumin (0.2 mg/ml vs. 0.6 mg/ml, P = 0.019 and 0.3 mg/ml vs. 0.6 mg/ml, P = 0.028), leukocytes (424 /ml vs. 1,430/ml; P = 0.016 and 768 /ml vs. 1,826/ml; P = 0.025), and lactate dehydrogenase activity (82 U/l vs. 232 U/l; P = 0.006 and 123 U/l vs. 303 U/l; P = 0.020). Thirty-day survival was associated with AQP5 -1364A/C genotypes (P = 0.005), with survival of 62% for AA genotypes (58 of 93) but 86% for C-allele carriers (37 of 43). Furthermore, multiple proportional hazard analysis revealed the AA genotype was at high risk for death within 30 days (hazard ratio, 3.53; 95% CI, 1.38 to 9.07; P = 0.009). CONCLUSIONS: In acute respiratory distress syndrome attributable to bacterial pneumonia, the C-allele of the AQP5 -1364A/C promoter polymorphism is associated with an attenuated pulmonary inflammation and higher 30-day survival. Thus, the AQP5 genotype impacts on inflammation and prognosis in acute respiratory distress syndrome.
我们对这个主题已经有了一定的了解：急性呼吸窘迫综合征是根据临床标准定义的，但缺乏精确的特征可能会导致负面的试验，并阻碍个性化护理。水通道蛋白-5（AQP5）的多态性是炎症的关键介质，可能会影响结果。
这篇文章告诉我们一些新的信息：在由细菌性肺炎引起的急性呼吸窘迫综合征中，AQP5-1364A/C 启动子多态性的 C 等位基因与较少的肺部炎症和更高的存活率相关。这可能会改善急性呼吸窘迫综合征的特征，并最终促进个体化护理。
背景：AQP5-1364A/C 启动子单核苷酸多态性与脓毒症中 AQP5 表达和死亡率的改变有关。因为 AQP5 表达改变中性粒细胞的迁移，所以它可能会影响细菌诱发的急性呼吸窘迫综合征中的肺部炎症和存活。因此，作者测试了以下假设：在由细菌引起的肺炎导致急性呼吸窘迫综合征的患者中，AC/CC 基因型与（1）减轻的肺部炎症和（2）更高的 30 天存活率相关。
方法：在这项前瞻性、观察性研究中，在入住重症监护病房后 24 小时内进行支气管肺泡灌洗和血液采样。在 136 名由细菌引起的急性呼吸窘迫综合征的白种人中，测量 AQP5-1364A/C 启动子多态性、支气管肺泡灌洗液总蛋白、白蛋白、白细胞浓度和乳酸脱氢酶活性的基因型，以评估基因型与存活率之间的关系。
结果：AC/CC 患者和幸存者的支气管肺泡灌洗液蛋白水平较低（0.9mg/ml 与 2.3mg/ml，P<0.001；1.6mg/ml 与 2.6mg/ml，P=0.035），白蛋白水平较低（0.2mg/ml 与 0.6mg/ml，P=0.019；0.3mg/ml 与 0.6mg/ml，P=0.028），白细胞计数较低（424/ml 与 1430/ml，P=0.016；768/ml 与 1826/ml，P=0.025），乳酸脱氢酶活性较低（82U/L 与 232U/L，P=0.006；123U/L 与 303U/L，P=0.020）。30 天存活率与 AQP5-1364A/C 基因型相关（P=0.005），AA 基因型的存活率为 62%（93 例中的 58 例），但 C 等位基因携带者的存活率为 86%（43 例中的 37 例）。此外，多比例风险分析显示，AA 基因型在 30 天内死亡的风险很高（危险比，3.53；95%CI，1.38 至 9.07；P=0.009）。
结论：在由细菌性肺炎引起的急性呼吸窘迫综合征中，AQP5-1364A/C 启动子多态性的 C 等位基因与减轻的肺部炎症和较高的 30 天存活率相关。因此，AQP5 基因型对急性呼吸窘迫综合征的炎症和预后有影响。
Int J Mol Sci. 2022-10-5
ISRN Otolaryngol. 2012-10-16
Life (Basel). 2024-12-20
Front Immunol. 2024
Int J Mol Sci. 2023-12-29
Int J Mol Sci. 2023-1-18
Comput Math Methods Med. 2022
J Inflamm Res. 2022-6-15
Int J Mol Sci. 2021-2-8
Zotero 插件