Second Department of Respiratory Medicine.
First Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2017 Dec 6;12:3511-3521. doi: 10.2147/COPD.S152134. eCollection 2017.
Metabolomics is the global unbiased analysis of all the small-molecule metabolites within a biological system. Metabolic profiling of different high-resolution computed tomography (HRCT) phenotypes of COPD patients before and after treatment may identify discriminatory metabolites that can serve as biomarkers and therapeutic agents.
H nuclear magnetic resonance spectroscopy (H-NMR)-based metabolomics was performed on a discovery set of plasma samples from 50 patients with stable COPD. Patients were assigned into two groups on the basis of HRCT findings including phenotype E (n=22) and phenotype M (n=28). After budesonide-formoterol treatment (160/4.5 µg ×2 inhalations twice daily for 3 months), clinical characteristics and metabolites were then compared between phenotype E pretreatment and posttreatment, phenotype M pretreatment and posttreatment, phenotype E pretreatment and phenotype M pretreatment, and phenotype E posttreatment and phenotype M posttreatment.
Inhaled budesonide-formoterol therapy for both phenotype E (emphysema without bronchial wall thickening) and phenotype M (emphysema with bronchial wall thickening) was effective. However, phenotype E and phenotype M were different in response to therapy. Patients with phenotype M in response to therapeutic effects were significantly greater compared with phenotype E. Certain metabolites were identified, which were closely related to the treatment and phenotype. Metabolic changes in phenotype E or phenotype M after treatment may be involved with adenosine diphosphate (ADP), guanosine, choline, malonate, tyrosine, glycine, proline, l-alanine, l-valine, l-threonine leucine, uridine, pyruvic acid, acetone and metabolism disturbance. Metabolic differences between phenotype E and phenotype M in pretreatment and posttreatment covered glycine, d-glucose, pyruvic acid, succinate, lactate, proline, l-valine and leucine.
Bronchial wall thickening in COPD may be an indicator for predicting the better response to the treatment with bronchodilator and corticosteroid. The identification of metabolic alterations provides new insights into different HRCT phenotypes and therapeutic assessment of COPD.
代谢组学是对生物系统内所有小分子代谢物进行的全面、无偏分析。对不同治疗前后慢性阻塞性肺疾病（COPD）患者高分辨率计算机断层扫描（HRCT）表型的代谢谱进行分析，可能会发现可作为生物标志物和治疗药物的有区别的代谢物。
对 50 例稳定期 COPD 患者的血浆样本进行基于 H 磁共振波谱（H-NMR）的代谢组学分析。根据 HRCT 结果，将患者分为两组，包括表型 E（n=22）和表型 M（n=28）。在布地奈德福莫特罗治疗（160/4.5μg×2 吸入，每日两次，持续 3 个月）后，比较表型 E 治疗前后、表型 M 治疗前后、表型 E 治疗前与表型 M 治疗前以及表型 E 治疗后与表型 M 治疗后的临床特征和代谢物。
吸入布地奈德福莫特罗治疗对表型 E（无支气管壁增厚的肺气肿）和表型 M（有支气管壁增厚的肺气肿）均有效。然而，表型 E 和表型 M 对治疗的反应不同。对治疗有反应的表型 M 患者明显多于表型 E。确定了某些与治疗和表型密切相关的代谢物。治疗后表型 E 或表型 M 的代谢变化可能与二磷酸腺苷（ADP）、鸟苷、胆碱、丙二酸盐、酪氨酸、甘氨酸、脯氨酸、亮氨酸、缬氨酸、苏氨酸、亮氨酸、尿苷、丙酮酸、丙酮和代谢紊乱有关。治疗前后表型 E 和表型 M 之间的代谢差异涵盖了甘氨酸、d-葡萄糖、丙酮酸、琥珀酸、乳酸、脯氨酸、缬氨酸和亮氨酸。
COPD 中的支气管壁增厚可能是预测对支气管扩张剂和皮质类固醇治疗反应更好的指标。代谢改变的鉴定为 COPD 的不同 HRCT 表型和治疗评估提供了新的见解。
