Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

Abstract

High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.

Effects of Tao‐Hong‐Si‐Wu decoction on acute blood stasis in rats based on a LC‐Q/TOF‐MS metabolomics and network approach

“…Commonly, R 2 Y provides an estimate of how well the model fits the Y data, and Q 2 is an estimate of how well the model predicts the X . To gain a high predictive ability, the R 2 Y and Q 2 values should be close to 1 (Guo et al, ). The R 2 Y of the PLS‐DA model in positive and negative modes was 0.986 and 0.858, and the Q 2 was 0.957 and 0.829, respectively.…”

“…Log2‐fold change was used to show how these selected differential metabolites varied between groups. Univariate and multivariate statistical analyses showed that significantly changed metabolites distinguishing acute blood stasis model from normal control rats were acquired on the condition of p < 0.05, fold change (FC) <0.8 or >1.2, and VIP > 1(Guo et al, ; Wiklund et al, ).…”

Deciphering Molecular Cascades in a Novel Acclimatization Strategy for Rapid Ascent to High Altitude

“…HAPE patients whose metabolome was analyzed were found to have dysregulated glycolysis and upregulated protein catabolic processes [55, 56]. The analysis of lung proteome also revealed extensive perturbations in metabolic pathways and bio-energetics.…”

Telomere length‐related gene ACYP2 polymorphism is associated with the risk of HAPE in Chinese Han population

“…HAPE usually occurs in plainsmen who go to a plateau or in plateau residents who climb to a higher altitude, with symptoms of cough, dyspnea, chest distress and easily becoming fatigued . The risk factors of HAPE may include male sex, high altitude, rapid ascent, hypoxia and a possible genetic predisposition to HAPE . However, the exact mechanisms underlying the pathogenesis of HAPE are still unclear.…”