Abstract

Introduction

Obstructive sleep apnea (OSA) is a common sleep breathing disorder with significant public health consequences. Despite this, no clinically available objective molecular biomarkers to diagnose, risk stratify and quantify treatment efficiency exist. To this end, high-throughput metabolomics data could serve as a valuable quantitative tool.

Methods

We designed a pilot study to investigate the metabolomic effects of OSA and CPAP treatment. Blood serum samples were collected from OSA patients and healthy controls matched with respect to age (±5 years), BMI (±2.5 kg/m²) and gender (N = 20/group). Samples from OSA patients were obtained before and after continuous positive airway pressure (CPAP) treatment. Polar metabolites were analyzed using a targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics technique.

Results

Supervised multivariate analysis using serum metabolic values of OSA patients and healthy controls showed a significantly different overall metabolic profile between the two groups (orthogonal partial least squares discriminant analysis [OPLS-DA] Q²=0.25, p=0.04). Acetylornithine, choline, cytidine, dodecenoylcarnitine, methionine sulfoxide and 3-indoxylsulfate were among the most perturbed metabolites. Major metabolic pathways altered in the OSA patients were methionine and phospholipid metabolism, as well as gut microbial co-metabolism. Lysophosphatidylcholine (16:0), a phospholipid metabolite, demonstrated significant linear association with improved oxygen saturation nadir post CPAP treatment (R² = 0.57), suggesting the metabolic features may be used as prognostic clinical biomarkers.

Conclusion

These results suggest that OSA significantly impacts blood metabolites, which could potentially be used to establish OSA biomarkers. Moreover, specific metabolic features are associated with post CPAP improvement, such as phospholipids, suggesting a functional association of these metabolites that may help us understand the heterogeneity of OSA. Overall, these results demonstrate the potential of metabolic profiling to develop quantitative molecular markers of OSA. Further studies are underway to validate these findings and investigate the utility of metabolic profiles to objectively measure CPAP efficacy.

Support

The work was supported by the program project grant P01 HL094307.

中文翻译：

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0054阻塞性睡眠呼吸暂停的代谢产物特征使病例与对照不同，并通过CPAP改善

摘要

介绍

阻塞性睡眠呼吸暂停（OSA）是一种常见的睡眠呼吸障碍，具有重大的公共卫生后果。尽管如此，尚不存在可用于诊断，风险分层和量化治疗效率的临床上可用的客观分子生物标记。为此，高通量代谢组学数据可以作为有价值的定量工具。

方法

我们设计了一项初步研究，以研究OSA和CPAP治疗的代谢组学影响。从OSA患者和健康对照组收集血清样本，这些样本的年龄（±5岁），BMI（±2.5 kg / m ²）和性别（N = 20 /组）相匹配。在连续气道正压（CPAP）治疗之前和之后，从OSA患者中获取样品。使用靶向超高效液相色谱-串联质谱（UPLC-MS / MS）代谢组学技术分析极性代谢物。

结果

使用OSA患者和健康对照组的血清代谢值进行的监督多变量分析显示，两组之间的总体代谢特征显着不同（正交偏最小二乘判别分析[OPLS-DA] Q ² = 0.25，p = 0.04）。乙酰基鸟氨酸，胆碱，胞苷，十二碳酰肉碱，蛋氨酸亚砜和3-吲哚基硫酸盐是最易受干扰的代谢物。OSA患者中改变的主要代谢途径是蛋氨酸和磷脂代谢，以及肠道微生物共代谢。CPAP治疗后，磷脂代谢产物溶血磷脂酰胆碱（16：0）与改善的血氧饱和度呈显着线性关联（R ² = 0.57），表明代谢功能可以用作预后的临床生物标志物。

结论

这些结果表明，OSA显着影响血液代谢产物，可潜在地用于建立OSA生物标志物。此外，特定的代谢功能与CPAP的改善相关，例如磷脂，表明这些代谢物的功能关联可能有助于我们了解OSA的异质性。总体而言，这些结果证明了代谢谱分析开发OSA定量分子标志物的潜力。正在进行进一步的研究以验证这些发现，并研究代谢谱在客观上测量CPAP疗效的效用。

支持

这项工作得到了计划项目拨款P01 HL094307的支持。