Syndrome Markers Of Infantile Bronchial Asthma In Metabonomics

Bronchial asthma is one of the most common chronic diseases that threaten children’s health.Due to the environmental deterioration,lifestyle changes and other factors,the incidence of bronchial asthma in children is increasing year by year,resulting in a huge burden on the family.Traditional Chinese medicine(TCM)has a long history and obvious curative effect on children’s asthma with perfect theory,method,prescription and medicine system.The differentiation of children’s asthma can be divided into three stages including the onset deferment period and remission stage,eight syndromes including Wind-cold evil tightening Fei,Phlegm-heat obstructing Fei syndrome and so on.In clinical work,the judgment of asthma differentiation is based on the doctor’s personal experience,yet there is still lack of objective indicators to distinguish different syndromes.Syndrome is a special term of TCM,which is in the core position of the whole theory in TCM.To accelerate the standardization of TCM syndrome and to realize the objectivity of TCM syndrome is the prerequisite for the scientific development of TCM.This study is based on objectification and standardization of TCM syndromes,taking bronchial asthma in children as the breakthrough point,using metabonomics technology to reveal the material basis of different syndromes in children’s asthma to provide a reference for the microscopic characterization of TCM syndromes.Object:By analysing urine metabolic profiles of Phlegm-heat obstructing Fei syndrome(PHOFS)and non-PHOFS on exacerbated asthma and Fei-Pi Qi deficiency syndrome(FPQDS)on remission stage to explore potential metabolic biomarkers in different syndromes of asthma in children.Methods:Twenty-four sick children with PHOFS,twenty sick children with non-PHOFS in exacerbation,and forty sick children with FPQDS in remission stage were enrolled.Another twenty-nine healthy children were collected.Their urine specimens were all detected by gas chromatography-mass spectrometer/mass spectrometer(GC-MS/MS).Additional,the specimens of PHOFS and non-PHOFS were detected by liquid chromatography-mass spectrometer/mass spectrometer(LC-MS/MS).The obtained data were analyzed with orthogonal partial least squares-discriminant analysis(OPLS-DA).Differential metabolites between groups screened and identified through the variable importance in the projection(VIP),non parametric test and XCMS Online analysis platform.At the same time,MetaboAnalyst platform was used to analyze the abnormal metabolic pathway.Results:Clear separations existed.Different metabolites and several metabolic pathways were identified.1.Compared with the normal group,contents of fourteen substances like urinary uric acid,stearic acid,inositol decreased,and aminomalonic acid increased in exacerbation.The process was mainly involved in five metabolic pathways such as lysine degradation and biosynthesis,pyruvate metabolism.2.Compared with non-PHOFS in exacerbation,by GC-MS/MS,contents of nine substances like oxalic acid,L-threonine,pyrimidine decreased,and four metabolic pathways such as pentose phosphate pathway,inositol phosphate metabolism were identified with PHOFS.By LC-MS/MS,the levels of organic acids,amino acids,fat,ketone compound such as methionine,succinic acid,lysine,creatine,kynurenine,and cyclic AMP were upregulated,and only hydroxy indole acetaldehyde went down.Furthermore,five abnormal metabolic pathways,such as biotin metabolism,tryptophan metabolism were identified in PHOFS.3.Compared with FPQDS in remission stage,contents of eight substances like Amino malonic acid,proline,phenylalanine,hexadecanoic acid were increased whereas myo-inositol,uric acid,and octadecanoic acid were decreased in the urine of children with PHOFS.Furthermore,the metabolic pathways for arginine and proline,glycine,serine and threonine,inositol phosphate,and phenylalanine were identified as abnormal pathways.Conlusion:Urine metabolites in infantile bronchial asthma episode and health children are different and different syndromes of bronchial asthma episode and different syndromes of asthma in different periods exists the basis of metabolic biomarkers and pathways,which may be the essence of different syndromes in TCM.Through further verification and optimization,the metabolite can be used as a biological marker of TCM Syndromes of bronchial asthma in children.