Serum Metabolomics Analysis of Asthma in Different Inflammatory Phenotypes: A Cross-Sectional Study in Northeast China

Abstract

Background and Objective Asthma as a chronic heterogeneous disease seriously affects the quality of life. Incorrect identification for its clinical phenotypes lead to a huge waste of medical resources. Metabolomic technique as a novel approach to explore the pathogenesis of diseases have not been used to study asthma based on their clear defined inflammatory phenotypes. This study is aimed to distinguish the divergent metabolic profile in different asthma phenotypes and clarify the pathogenesis of them. Methods Participants including eosinophilic asthmatics (EA, n=13), noneosinophilic asthmatics (NEA, n=16), and healthy controls (HC, n=15) were enrolled. A global profile of untargeted serum metabolomics was identified with Ultra Performance Liquid Chromatography–Mass Spectrometry technique. Results Multivariate analysis was performed and showed a clear distinction between EA, NEA, and HC. A total of 18 different metabolites were recognized between the three groups based on OPLS-DA model and involved in 10 perturbed metabolic pathways. Glycerophospholipid metabolism, retinol metabolism, and sphingolipid metabolism were identified as the most significant changed three pathways (impact > 0.1 and -log(P) > 4) between the phenotypes. Conclusions We showed that the different inflammatory phenotypes of asthma involve the immune regulation, energy, and nutrients metabolism. The clarified metabolic profile contributes to understanding the pathophysiology of asthma phenotypes and optimizing the therapeutic strategy against asthma heterogeneity.

Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism

“…Systematic metabolomics displayed a significant difference in metabolic profiles between the experimental murine asthmatic phenotypes, which is consistent with our research on clinical samples [28]. According to the fitting degree of OPLS-DA models, we discovered that compared to HC, NEA seemed to be perturbed at a larger scale than EA.…”

“…Similar to our previous report on the metabolic features of clinical asthmatic patients, roles in linoleic acid, glycerophospholipid, and retinol metabolism were also discovered in murine models [28]. The intervention on primary bile acid metabolism may be related with the pharmacological effect of RWC on other organs.…”

“…Various metabolites such as amino acids and phospholipids have been identified [26,27]. Differences in metabolic profile between the asthmatic phenotypes have also been confirmed by our team [28]. Environmental factors and metabolic markers in vivo of asthma might be novel points to illustrate the pathogenesis of asthmatic phenotypes and the possible pharmacological mechanism of a potential medicine for asthmatic therapy.…”

“…Serum and BALF samples were prepared as previously described [28,72]. Briefly, the protein was precipitated and removed with acetonitrile.…”

“…The Waters Xevo G2-S Quadrupole Time-of-Flight (QTOF) mass spectrometer coupled with a UPLC system (Waters ACQUITY UPLC system and BEH C18 column, 2.1 mm × 100 mm, 1.7 mm, Waters Corporation, Milford, MA, USA), as described in our previous study [28], was used here with the parameters of the UPLC-Q/TOF-MS/MS system set as before [28]. Data of the samples were collected in ESI+ mode.…”