Wendt Chris H, Nelsestuen Gary, Harvey Stephen, Gulcev Makedonka, Stone Matthew, Reilly Cavan
Department of Medicine, VA Medical Center, Minneapolis, MN, 55417, United States of America.
Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, United States of America.
PLoS One. 2016 May 26;11(5):e0155724. doi: 10.1371/journal.pone.0155724. eCollection 2016.
Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease with a significant public health burden. Currently there is no biomarker that identifies those at risk of developing COPD, progression of disease or disease phenotypes. We performed metabolomic profiling of bronchoalveolar lavage fluid (BALF) from COPD patients to determine if metabolites correlated with clinical measurements such as lung function, functional status and degree of emphysema.
Metabolomic components of BALF from 59 subjects with COPD and 20 healthy controls were separated by reversed-phase UPLC and analyzed by ESI-ToF mass spectrometry. We used univariate analysis and multiple regression models to investigate associations between metabolomic features and various clinical variables, such as lung function, functional status as measured by the St. George Respiratory Quotient Score and emphysema as measured by the CT density mask score.
We identified over 3900 features by mass spectrometry, many consistent with peptides. Subjects with severe COPD had increased concentration of peptides compared to controls (p < 9.526e-05). The peptide concentration correlated with spirometry, specifically pulmonary function tests associated with airflow obstruction. There was no correlation with CT density, i.e. emphysema, or functional status.
Metabolomic profiling of BALF in COPD patients demonstrated a significant increase in peptides compared to healthy controls that associated strongly to lung function, but not emphysema or functional status.
慢性阻塞性肺疾病（COPD）是一种具有重大公共卫生负担的异质性疾病。目前尚无生物标志物可识别有患COPD风险、疾病进展或疾病表型的人群。我们对COPD患者的支气管肺泡灌洗液（BALF）进行了代谢组学分析，以确定代谢物是否与诸如肺功能、功能状态和肺气肿程度等临床指标相关。
采用反相超高效液相色谱法分离59例COPD患者和20名健康对照者的BALF代谢组学成分，并通过电喷雾电离飞行时间质谱法进行分析。我们使用单变量分析和多元回归模型来研究代谢组学特征与各种临床变量之间的关联，这些临床变量包括肺功能、用圣乔治呼吸商评分衡量的功能状态以及用CT密度掩码评分衡量的肺气肿。
我们通过质谱鉴定出3900多个特征，其中许多与肽类一致。与对照组相比，重度COPD患者的肽浓度升高（p < 9.526e-05）。肽浓度与肺量计测量结果相关，特别是与气流阻塞相关的肺功能测试。与CT密度（即肺气肿）或功能状态无关。
COPD患者BALF的代谢组学分析表明，与健康对照相比，肽类显著增加，且与肺功能密切相关，但与肺气肿或功能状态无关。
