Personalised therapeutic management of epileptic patients guided by pathway-driven breath metabolomics

ABSTRACT:

BACKGROUND: Therapeutic management of epilepsy remains a challenge, since optimal systemic antiseizure medication (ASM) concentrations do not always correlate with improved clinical outcome and minimal side effects. We tested the feasibility of non-invasive real-time breath metabolomics as an extension of traditional therapeutic drug monitoring for patient-stratification by simultaneously monitoring drug-related and drug-modulated metabolites.

METHODS: This proof-of-principle observational study involved 93 breath measurements of 54 paediatric patients monitored over a period of 2.5 years, along with an adults’ cohort of 37 patients measured in two different hospitals. Exhaled breath metabolome of epileptic patients was measured in real-time using secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS).

RESULTS: We show that systemic ASM concentrations could be predicted by the breath test. Total and free valproic acid (VPA; an ASM) is predicted with concordance correlation coefficient (CCC) of 0.63 and 0.66, respectively. We also find i) high between- and within-subject heterogeneity in VPA metabolism; ii) several amino acid metabolic pathways are significantly enriched (p < 0.01) in patients suffering from side effects and iii) tyrosine metabolism is significantly enriched (p < 0.001), with downregulated pathway compounds in non-responders.

CONCLUSIONS: These results show that real-time breath analysis of epileptic patients provides reliable estimations of systemic drug concentrations along with risk estimates for drug response and side effects.

INSTRUMENT(S): Direct infusion MS - positive, Direct infusion MS - negative

PROVIDER: MTBLS2400 | MetaboLights | 2021-06-21

REPOSITORIES: MetaboLights