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Disruption of histidine and energy homeostasis in chronic obstructive pulmonary disease.

ABSTRACT: Background:Chronic obstructive pulmonary disease (COPD) is a systemic condition that is too complex to be assessed by lung function alone. Metabolomics has the potential to help understand the mechanistic underpinnings that contribute to COPD pathogenesis. Since blood metabolomics may be affected by sex and body mass index (BMI), the aim of this study was to determine the metabolomic variability in male smokers with and without COPD who have a narrow BMI range. Methods:We compared the quantitative proton nuclear magnetic resonance acquired serum metabolomics of a male Chinese Han population of non-smokers without COPD, and smokers with and without COPD. We also assessed the impact of smoking status on metabolite concentrations and the associations between metabolite concentrations and inflammatory markers such as serum interleukin-6 and histamine, and blood cell differential (%). Metabolomics data were log-transformed and auto-scaled for parametric statistical analysis. Mean normalized metabolite concentration values and continuous demographic variables were compared by Student's t-test with Welch correction or ANOVA with post-hoc Tukey's test, as applicable; t-test p-values for metabolomics data were corrected for false discovery rate (FDR). A Pearson association matrix was built to evaluate the relationship between metabolite concentrations, clinical parameters and markers of inflammation. Results:Twenty-eight metabolites were identified and quantified. Creatine, glycine, histidine, and threonine concentrations were reduced in COPD patients compared to non-COPD smokers (FDR ?15%). Concentrations of these metabolites were inversely correlated with interleukin-6 levels. COPD patients had overall dampening of metabolite concentrations including energy-related metabolic pathways such as creatine metabolism. They also had higher histamine levels and percent basophils compared to smokers without COPD. Conclusion:COPD is associated with alterations in the serum metabolome, including a disruption in the histidine-histamine and creatine metabolic pathways. These findings support the use of metabolomics to understand the pathogenic mechanisms involved in COPD.Trial registration www.clinicaltrials.gov, NCT03310177.

SUBMITTER: Diao W

PROVIDER: S-EPMC6732562 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Disruption of histidine and energy homeostasis in chronic obstructive pulmonary disease.

Diao Wenqi W Labaki Wassim W WW Han MeiLan K MK Yeomans Larisa L Sun Yihan Y Smiley Zyad Z Kim Jae Hyun JH McHugh Cora C Xiang Pingchao P Shen Ning N Sun Xiaoyan X Guo Chenxia C Lu Ming M Standiford Theodore J TJ He Bei B Stringer Kathleen A KA

International journal of chronic obstructive pulmonary disease 20190903

<h4>Background</h4>Chronic obstructive pulmonary disease (COPD) is a systemic condition that is too complex to be assessed by lung function alone. Metabolomics has the potential to help understand the mechanistic underpinnings that contribute to COPD pathogenesis. Since blood metabolomics may be affected by sex and body mass index (BMI), the aim of this study was to determine the metabolomic variability in male smokers with and without COPD who have a narrow BMI range.<h4>Methods</h4>We compared ...[more]

PMID: 31564849

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Project description:BACKGROUND:Mild cognitive impairment is a common systemic manifestation of chronic obstructive pulmonary disease (COPD). However, its pathophysiological origins are not understood. Since, cognitive function relies on efficient communication between distributed cortical and subcortical regions, we investigated whether people with COPD have disruption in white matter connectivity. METHODS:Structural networks were constructed for 30 COPD patients (aged 54-84 years, 57% male, FEV1 52.5% pred.) and 23 controls (aged 51-81 years, 48% Male). Networks comprised 90 grey matter regions (nodes) interconnected by white mater fibre tracts traced using deterministic tractography (edges). Edges were weighted by the number of streamlines adjusted for a) streamline length and b) end-node volume. White matter connectivity was quantified using global and nodal graph metrics which characterised the networks connection density, connection strength, segregation, integration, nodal influence and small-worldness. Between-group differences in white matter connectivity and within-group associations with cognitive function and disease severity were tested. RESULTS:COPD patients' brain networks had significantly lower global connection strength (p = 0.03) and connection density (p = 0.04). There was a trend towards COPD patients having a reduction in nodal connection density and connection strength across the majority of network nodes but this only reached significance for connection density in the right superior temporal gyrus (p = 0.02) and did not survive correction for end-node volume. There were no other significant global or nodal network differences or within-group associations with disease severity or cognitive function. CONCLUSION:COPD brain networks show evidence of damage compared to controls with a reduced number and strength of connections. This loss of connectivity was not sufficient to disrupt the overall efficiency of network organisation, suggesting that it has redundant capacity that makes it resilient to damage, which may explain why cognitive dysfunction is not severe. This might also explain why no direct relationships could be found with cognitive measures. Smoking and hypertension are known to have deleterious effects on the brain. These confounding effects could not be excluded.

Dataset Information

Disruption of histidine and energy homeostasis in chronic obstructive pulmonary disease.

Publications

Disruption of histidine and energy homeostasis in chronic obstructive pulmonary disease.

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