Metabolomics Identifies Novel Blood Biomarkers of Pulmonary Function and COPD in the General Population.

Bing Yu,Stephanie London,Annah Wyss,Claudia Flexeder,Alanna Morrison,Kari North,Karsten Suhre,Gregory Michelotti,Stefan Karrasch,Gregory Wagner,Holger Schulz,Robert Mohney,Christian Gieger,Robert Mcgarrah,Gabi Kastenmüller,Eric Boerwinkle,Annette Peters

doi:10.3390/metabo9040061

Abstract

Determination of metabolomic signatures of pulmonary function and chronic obstructive pulmonary disease (COPD) in the general population could aid in identification and understanding of early disease processes. Metabolome measurements were performed on serum from 4742 individuals (2354 African-Americans and 1529 European-Americans from the Atherosclerosis Risk in Communities study and 859 Europeans from the Cooperative Health Research in the Region of Augsburg study). We examined 368 metabolites in relation to cross-sectional measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio (FEV1/FVC) and COPD using multivariable regression followed by meta-analysis. At a false discovery rate of 0.05, 95 metabolites were associated with FEV1 and 100 with FVC (73 overlapping), including inverse associations with branched-chain amino acids and positive associations with glutamine. Ten metabolites were associated with FEV1/FVC and seventeen with COPD (393 cases). Enriched pathways of amino acid metabolism were identified. Associations with FEV1 and FVC were not driven by individuals with COPD. We identified novel metabolic signatures of pulmonary function and COPD in African and European ancestry populations. These may allow development of biomarkers in the general population of early disease pathogenesis, before pulmonary function has decreased to levels diagnostic for COPD.

Highlights

Pulmonary function, as assessed by forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC (FEV1/FVC), reflects the physiological state of the lung
Given the large number of findings, in the main text tables, we show only the top 20 associations that meet Bonferroni correction where the metabolite was measured in all three datasets (Table 2 for FEV1 and Table 3 for FVC); all metabolites associated at false discovery rate (FDR) < 0.05 are in Table S1 for FEV1 and Table S2 for FVC
By combining data from over 4700 individuals across two population-based studies, encompassing both African-American and European ancestry, we identified numerous metabolites related to quantitative pulmonary function measures

Summary

Introduction

As assessed by forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC (FEV1/FVC), reflects the physiological state of the lung. These measures are used to diagnose and monitor chronic obstructive pulmonary disease (COPD). Reduced pulmonary function in the general population correlates with systemic inflammation biomarkers [1,2]. Lower pulmonary function is a risk factor for mortality in the general population, independently of smoking and other risk factors and even among individuals with normal spirometry [10,11,12,13]. The underlying mechanisms for these diverse impacts of reductions in pulmonary function remain unknown

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Conclusion