Eicosanoids metabolized through LOX distinguish asthma–COPD overlap from COPD by metabolomics study

Chuanxu Cai,1,2,* Xiqing Bian,3,* Mingshan Xue,1 Xiaoqing Liu,1 Haisheng Hu,1 Jingxian Wang,4 Song Guo Zheng,5 Baoqing Sun,1 Jian-Lin Wu31Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Laboratory Medicine, Shenzhen People’s Hospital, Shenzhen, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macao, People’s Republic of China; 4Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 5Department of Internal Medicine, Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, USA*These authors contributed equally to this workBackground and objective: The prevalence of asthma is greater than 20% in patients previously diagnosed with COPD. Patients with asthma–COPD overlap (ACO) are at risk of rapid progression of disease and severe exacerbations. However, in some patients with ACO, a clear distinction from COPD is very difficult by using physiological testing techniques. This study aimed to apply a novel metabolomic approach to identify the metabolites in sera in order to distinguish ACO from COPD.Methods: In the study, blood samples were collected from patients with COPD, ACO, and healthy controls. Cholamine derivatization-ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to investigate serum metabolites of eicosanoids.Results: A clear intergroup separation existed between the patients with ACO and those with COPD, while ACO tends to have higher serum metabolic levels of eicosanoids. A robust Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA) model was found for discriminating between ACO and COPD (R2Y =0.81, Q2=0.79). In addition, there is a significant correlation between some metabolites and clinical indicators, such as hydroxyeicosatetraenoic acids (HETEs), hydroperoxyeicosatetraenoic acids (HPETEs) and FEV1/FVC. The higher values of area under the receiver operating characteristic curves (ROC) of HETEs, which were metabolized from HPETEs through lipoxygenase (LOX), indicated that they should be the potential biomarkers to distinguish ACO from COPD.Conclusion: Eicosanoids can clearly discriminate different biochemical metabolic profiles between ACO and COPD. The results possibly provide a new perspective to identify potential biomarkers of ACO and may be helpful for personalized treatment.Keywords: metabolomics, COPD, asthma–COPD overlap, cholamine derivatization-UHPLC-Q-TOF/MS