Study On Serum Metabolic Markers After Inhalation Of Tiotropium In Patients With Chronic Obstructive Pulmonary Disease Of Different Imaging Phenotypes

Objectives:In this study,we used nuclear magnetic resonance(NMR)metabolomics research methods to compare E-type chronic obstructive pulmonary disease(COPD),M-type COPD inhalation tiotropium treatment 3 months ago And then with the normal control group of serum metabolic profile,screening serum metabolic markers and to explore its clinical value.Methods:The fasting serum samples were collected from patients with E-type COPD patients(10 cases),M-type COPD patiens(10 cases)and normal healthy people(10 cases)in the First Affiliated Hospital of Kunming Medical University from october 2015 to october 2016,1H-NMR technique was used to analyze the serum samples of each group.Import the original data into the SIMCA-P+ software,the principal component analysis(PCA)and orthogonal partial least squares(OPLS-DA)were used to model the date,and the most influential metabolites were screened out based on variable importance for projection(VIP).Univariate analysis was performed on selected metabolites for further selections of metabolites,which,the fold change of concentration is greater than 2 and the difference is statistically significant(P<0.05).Then,the metabolic markers were selected by chenomx NMR suite software,according to domestic and foreign research.Results:1.Comparison of serum metabolites in E-type COPD inhaled tiotropium group before and after treatment with normal control group:pattern recognition analysis established model can distinguish between two groups.E-type COPD patients with tiotropium in the treatment group before and the normal control group serum metabolites were detected 18 kinds of metabolites,E-type COPD patients with tiotropium in the treatment group and the normal control group serum metabolites compared to 12 Metabolites.Ornithine,L-proline,2-hydroxyisobutyrate,lactic acid,lipid decreased before treatment with tiotropium,and increased after treatment;and lipoprotein,phenylalanine,tryptophan Concentration increased before treatment,decreased after treatment.2.Comparison of serum metabolites in M-type COPD inhaled tiotropium group before and after treatment with normal control group:pattern recognition analysis established model can distinguish between two groups.M-type COPD patients with tiotropium in the treatment group before and the normal control group serum metabolites were detected 21 kinds of metabolites,M-type COPD patients inhaled tiotropium treatment group and normal control group serum metabolites compared to 18 Metabolites.D-glucose decreased before treatment with tiotropium,and increased after treatment,while L-valine increased before treatment,decreased after treatment,and no change.3.E-type COPD patients after treatment group and the treatment group before the serum metabolite contrast:pattern recognition analysis established model can distinguish between two groups.The contents of L-alanine,glycine,phenylalanine,tyrosine,citric acid,lactic acid and pyridoxine succinic acid were decreased in the treatment group,and the concentration of choline and pyridoxine was increased high.4.M-type COPD patients after treatment group and the treatment group before the serum metabolite contrast:pattern recognition analysis established model can distinguish between two groups.four metabolites were detected.The concentration of tryptophan,inosinic acid and acetone decreased in the group of M-type COPD,and the concentration of ornithine increased.Conclusions:Through the metabolomics study based on nuclear magnetic resonance,the model established by metabolic profile can distinguish between E-type,M-type COPD patients and normal control group,E-type COPD patients inhaled tiotropium group before and after treatment,M Type of COPD group before and after treatment of serum metabolic.There were significant differences between the two groups before and after treatment,and the metabolites with specific changes in the two groups had different trends in the treatment of COPD patients.The concentration of metabolites was expected to be treated by individual treatment of the COPD.