Viswan Akhila, Singh Chandan, Rai Ratan Kumar, Azim Afzal, Sinha Neeraj, Baronia Arvind Kumar
Centre of Biomedical Research, Lucknow, Uttar Pradesh, India.
Faculty of Engineering and Technology, Dr. A. P. J Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India.
PLoS One. 2017 Nov 2;12(11):e0187545. doi: 10.1371/journal.pone.0187545. eCollection 2017.
Despite advancements in ventilator technologies, lung supportive and rescue therapies, the outcome and prognostication in acute respiratory distress syndrome (ARDS) remains incremental and ambiguous. Metabolomics is a potential insightful measure to the diagnostic approaches practiced in critical disease settings. In our study patients diagnosed with mild and moderate/severe ARDS clinically governed by hypoxemic P/F ratio between 100-300 but with indistinct molecular phenotype were discriminated employing nuclear magnetic resonance (NMR) based metabolomics of mini bronchoalveolar lavage fluid (mBALF). Resulting biomarker prototype comprising six metabolites was substantiated highlighting ARDS susceptibility/recovery. Both the groups (mild and moderate/severe ARDS) showed distinct biochemical profile based on 83.3% classification by discriminant function analysis and cross validated accuracy of 91% using partial least squares discriminant analysis as major classifier. The predictive performance of narrowed down six metabolites were found analogous with chemometrics. The proposed biomarker model consisting of six metabolites proline, lysine/arginine, taurine, threonine and glutamate were found characteristic of ARDS sub-stages with aberrant metabolism observed mainly in arginine, proline metabolism, lysine synthesis and so forth correlating to diseased metabotype. Thus NMR based metabolomics has provided new insight into ARDS sub-stages and conclusively a precise biomarker model proposed, reflecting underlying metabolic dysfunction aiding prior clinical decision making.
尽管呼吸机技术、肺部支持和抢救治疗取得了进展，但急性呼吸窘迫综合征（ARDS）的治疗结果和预后仍然难以确定且不明确。代谢组学是一种在危重病诊断方法中具有潜在洞察力的测量手段。在我们的研究中，对于临床上诊断为轻度和中度/重度ARDS的患者，其低氧血症P/F比值在100至300之间，但分子表型不明确，我们采用基于核磁共振（NMR）的微量支气管肺泡灌洗液（mBALF）代谢组学对其进行鉴别。包含六种代谢物的生物标志物原型得到了证实，突出了ARDS易感性/恢复情况。两组（轻度和中度/重度ARDS）基于判别函数分析的83.3%分类和使用偏最小二乘判别分析作为主要分类器的91%交叉验证准确率显示出不同的生化特征。发现六种代谢物经筛选后的预测性能与化学计量学相似。由脯氨酸、赖氨酸/精氨酸、牛磺酸、苏氨酸和谷氨酸六种代谢物组成的生物标志物模型被发现是ARDS亚阶段的特征，主要在精氨酸、脯氨酸代谢、赖氨酸合成等方面观察到代谢异常，与疾病代谢型相关。因此，基于NMR的代谢组学为ARDS亚阶段提供了新的见解，并最终提出了一个精确的生物标志物模型，反映了潜在的代谢功能障碍，有助于临床前期决策。
