Presenter Status

Fellow

Abstract Type

Research

Primary Mentor

Tamorah Lewis

Start Date

3-5-2022 11:30 AM

End Date

3-5-2022 1:30 PM

Presentation Type

Poster Presentation

Description

Background: Bronchopulmonary dysplasia (BPD) is one of the most common health complications of premature birth. Corticosteroids are commonly used for treatment of BPD, but their use is challenging due to variability in treatment response.

Objectives/Goal: Previous pharmacometabolomics study has established patterns of metabolite levels with response to dexamethasone. We obtained additional patient samples for metabolomics analysis to find associations between the metabolome and dexamethasone response in a validation cohort.

Methods/Design: 14 infants provided 15 plasma and 12 urine samples. The measure of treatment response was the calculated change in respiratory severity score (deltaRSS) from pre-to-post treatment. Each metabolite was assessed with paired analysis of pre and post-treatment samples using Wilcoxon signed rank test. Correlation analysis was conducted between deltaRSS and pre-to-post change in metabolite level.

Results: Analysis identified 20 plasma and 26 urine metabolites with significant level difference comparing pre to post treatment samples (p<0.05). 3 plasma and 4 urine metabolites were also significant in the original study. Pre-to-post treatment change in metabolite analysis found 4 plasma and 8 urine metabolites significantly associated with deltaRSS (p<0.05). Change in urine citrulline levels showed a similar correlation pattern with deltaRSS in the first study, with increasing level associated with improved drug response.

Conclusions: These results help validate the first major findings from pharmacometabolomics of BPD including key metabolites within the urea cycle and trans-4-hydroxyproline as a potential marker for lung injury. Ultimately, this study furthers our understanding of the mechanisms of steroid response in BPD patients. Future animal and mechanistic studies will augment our project.

MeSH Keywords

Metabolomics; Bronchopulmonary Dysplasia; Neonatology

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May 3rd, 11:30 AM May 3rd, 1:30 PM

Pharmacometabolomics Profiling of Preterm Infants Validates Patterns of Metabolism Associated with Response to Dexamethasone Treatment for Bronchopulmonary Dysplasia

Background: Bronchopulmonary dysplasia (BPD) is one of the most common health complications of premature birth. Corticosteroids are commonly used for treatment of BPD, but their use is challenging due to variability in treatment response.

Objectives/Goal: Previous pharmacometabolomics study has established patterns of metabolite levels with response to dexamethasone. We obtained additional patient samples for metabolomics analysis to find associations between the metabolome and dexamethasone response in a validation cohort.

Methods/Design: 14 infants provided 15 plasma and 12 urine samples. The measure of treatment response was the calculated change in respiratory severity score (deltaRSS) from pre-to-post treatment. Each metabolite was assessed with paired analysis of pre and post-treatment samples using Wilcoxon signed rank test. Correlation analysis was conducted between deltaRSS and pre-to-post change in metabolite level.

Results: Analysis identified 20 plasma and 26 urine metabolites with significant level difference comparing pre to post treatment samples (p<0.05). 3 plasma and 4 urine metabolites were also significant in the original study. Pre-to-post treatment change in metabolite analysis found 4 plasma and 8 urine metabolites significantly associated with deltaRSS (p<0.05). Change in urine citrulline levels showed a similar correlation pattern with deltaRSS in the first study, with increasing level associated with improved drug response.

Conclusions: These results help validate the first major findings from pharmacometabolomics of BPD including key metabolites within the urea cycle and trans-4-hydroxyproline as a potential marker for lung injury. Ultimately, this study furthers our understanding of the mechanisms of steroid response in BPD patients. Future animal and mechanistic studies will augment our project.

 

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