Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome
Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome
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DOI：
10.1186/s12931-014-0128-8
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发表时间：
2014-11-07
影响因子：
5.8
通讯作者：
Postle, Anthony D.
中科院分区：
文献类型：
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作者：
Dushianthan, Ahilanandan;Goss, Victoria;Postle, Anthony D.
背景资料：急性呼吸窘迫综合征（ARDS）是一种危及生命的危重疾病，其特征是与气道过早塌陷、气体交换异常和急性缺氧性呼吸衰竭相关的表面活性物质成分的定性和定量变化。表面活性剂代谢中这种失调的潜在机制尚未完全探索。缺乏临床试验的治疗效益，强调了详细的体内分析和表征的ARDS患者根据表面活性剂的合成和metabolish.Methods模式的重要性：10例中重度ARDS患者被招募。大多数人（90%）患有肺炎。分别于0、6、12、24、48、72和96 h给予氯化甲基-D9-胆碱（methyl-D9-choline chloride）灌胃，并抽取少量支气管肺泡灌洗液（BALF）。对照组为健康志愿者，在甲基-D9-胆碱输注后24和48小时进行BALF。组成分析和富集模式的稳定同位素标记的表面活性剂磷脂酰胆碱（PC）的测定通过电喷雾电离mass spectrometry.Results：减少总PC和分数PC 16：0/16：0浓度与健康对照组相比，ARDS患者的BALF。组成分析显示，减少分数组成的饱和PC物种与升高水平的较长的酰基链不饱和PC物种。新合成的PC组分的分子特异性显示出时程变化，在较早的时间点具有较低的PC 16：0/16：0组成，但在甲基-D9-胆碱输注后48小时与内源性组成达到接近平衡。甲基-D9-胆碱到表面活性剂总PC的富集在患者中几乎增加了一倍，具有相当大的变化individuals.Conclusions：这项研究表明，从ARDS患者中提取的表面活性剂PC的组成和动力学的显着改变。这种新的方法可能有助于根据表面活性剂的合成和代谢的ARDS患者的生化表型，使个性化的治疗方法，在未来的ARDS患者的管理。
Background: Acute respiratory distress syndrome (ARDS) is a life-threatening critical illness, characterised by qualitative and quantitative surfactant compositional changes associated with premature airway collapse, gas-exchange abnormalities and acute hypoxic respiratory failure. The underlying mechanisms for this dysregulation in surfactant metabolisms are not fully explored. Lack of therapeutic benefits from clinical trials, highlight the importance of detailed in-vivo analysis and characterisation of ARDS patients according to patterns of surfactant synthesis and metabolism.Methods: Ten patients with moderate to severe ARDS were recruited. Most (90%) suffered from pneumonia. They had an infusion of methyl-D9-choline chloride and small volume bronchoalveolar lavage fluid (BALF) was obtained at 0,6,12,24,48,72 and 96 hours. Controls were healthy volunteers, who had BALF at 24 and 48 hours after methyl-D9-choline infusion. Compositional analysis and enrichment patterns of stable isotope labelling of surfactant phosphatidylcholine (PC) was determined by electrospray ionisation mass spectrometry.Results: BALF of patients with ARDS consisted of diminished total PC and fractional PC16:0/16:0 concentrations compared to healthy controls. Compositional analysis revealed, reductions in fractional compositions of saturated PC species with elevated levels of longer acyl chain unsaturated PC species. Molecular specificity of newly synthesised PC fraction showed time course variation, with lower PC16:0/16: 0 composition at earlier time points, but achieved near equilibrium with endogenous composition at 48 hours after methyl-D9-choline infusion. The enrichment of methyl-D9-choline into surfactant total PC is nearly doubled in patients, with considerable variation between individuals.Conclusions: This study demonstrate significant alterations in composition and kinetics of surfactant PC extracted from ARDS patients. This novel approach may facilitate biochemical phenotyping of ARDS patients according to surfactant synthesis and metabolism, enabling individualised treatment approaches for the management of ARDS patients in the future.