Rationale: The biochemical mechanisms underlying lung function are incompletely understood.

Objectives: To identify and validate the plasma metabolome of lung function using two independent adult cohorts: discovery-the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk, n=10 460) and validation-the VA Normative Aging Study (NAS) metabolomic cohort (n=437).

Methods: We ran linear regression models for 693 metabolites to identify associations with forced expiratory volume in one second (FEV) and the ratio of FEV to forced vital capacity (FEV/FVC), in EPIC-Norfolk then validated significant findings in NAS. Significance in EPIC-Norfolk was denoted using an effective number of tests threshold of 95%; a metabolite was considered validated in NAS if the direction of effect was consistent and p<0.05.

Measurements And Main Results: Of 156 metabolites that associated with FEV in EPIC-Norfolk after adjustment for age, sex, body mass index, height, smoking and asthma status, 34 (21.8%) validated in NAS, including several metabolites involved in oxidative stress. When restricting the discovery sample to men only, a similar percentage, 18 of 79 significant metabolites (22.8%) were validated. A smaller number of metabolites were validated for FEV/FVC, 6 of 65 (9.2%) when including all EPIC-Norfolk as the discovery population, and 2 of 34 (5.9%) when restricting to men. These metabolites were characterised by involvement in respiratory track secretants. Interestingly, no metabolites were validated for both FEV and FEV/FVC.

Conclusions: The validation of metabolites associated with respiratory function can help to better understand mechanisms of lung health and may assist the development of biomarkers.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008068PMC
http://dx.doi.org/10.1136/thoraxjnl-2020-216639DOI Listing

Publication Analysis

Top Keywords

lung function
12
metabolomic differences
4
differences lung
4
function metrics
4
metrics evidence
4
evidence cohorts
4
cohorts rationale
4
rationale biochemical
4
biochemical mechanisms
4
mechanisms underlying
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!