Pneumologie 2013; 67 - P405
DOI: 10.1055/s-0033-1334761

Are metabolomic markers associated with spirometric lung function indices? Results of the KORAF4 Study

C Flexeder 1, S Karrasch 2, G Kastenmüller 1, C Meisinger 1, AP Petersen 1, C Prehn 1, R Wang-Sattler 1, S Weidinger 3, C Gieger 1, J Heinrich 1, R Holle 1, A Peters 1, T Illig 4, J Adamski 5, K Suhre 6, H Schulz 1
  • 1Helmholtz Zentrum München
  • 2Ludwig-Maximilians-University, München
  • 3University Hospital Schleswig-Holstein, Campus Kiel
  • 4Helmholtz Zentrum München, Hannover Medical School
  • 5Helmholtz Zentrum München, Technische Universität München
  • 6Helmholtz Zentrum München, Weill Cornell Medical College, Education City, Qatar

Aims: Respiratory function shows a large interindividual variability which is related to genetic, developmental and environmental factors. These determinants influence the individual's metabolism, but little is known about metabolic processes and lung function. Therefore, this study investigates the association between lung function indices and concentrations of metabolomic markers in adults from a population-based study.

Methods: Spirometry was performed in a subpopulation of the KORA-F4 cohort (Augsburg, Germany) comprising 1312 subjects aged 41 to 62 years. In fasting blood samples over 650 metabolites were determined on two different (a targeted and a non-targeted) mass spectrometry based metabolomics platforms. Linear regression models were calculated for each metabolite after adjustment for age, sex, smoking, body mass index (BMI) and batch effect and residuals of these models were used to assess the association between metabolites and percent predicted values for forced expiratory volume in 1 second (FEV1pp) and forced vital capacity (FVCpp), respectively.

Results: We identified a set of 17 metabolites which were significantly associated with lung function indices after correction for multiple testing (with p-values ranging from 3.29·10-4 to; 1.36·10-7). Thirteen of these metabolites showed a relationship with FVCpp whereas 15 metabolites were associated with FEV1pp. These indices are linked to different metabolites of the lipid metabolism (ten glycerophospholipids, three sphingolipids), to the tocopherol metabolism (gamma-tocopherol) and the tyrosine metabolism. Further, an association to xenobiotic pathway was observed (hippurate).

Conclusion: Our results suggest that metabolites from different pathways are associated with spirometric measures of lung function. Since lung surfactant is mainly composed of different phospholipids the lipid metabolites identified suggest the involvement of pulmonary surfactant. The observed association with the tocopherol metabolism may point towards the importance of antioxidant or anti-inflammatory defence for respiratory function.