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Exercise challenge amplifies differences in metabolomic signals between healthy smokers and smokers with COPD (gold2)

: Holz, Olaf; Roepcke, Stefan; Lauer, Gereon; Elmlinger, Martin; Lahu, Gezim; Hohlfeld, Jens Michael

American Journal of Respiratory and Critical Care Medicine 189 (2014), Art. A5952
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2014, San Diego/Calif.>
Fraunhofer ITEM ()

RATIONAL: COPD is often accompanied by a diminished exercise tolerance and reduced physical activity. To find novel COPD metabolome biomarkers we compared the serum of smokers with and without COPD after controlled food intake, before and after a period of fasting, and during and after exercise challenge to amplify potential pathophysiological biomarker signals.
METHODS: Twenty-four smokers with moderate COPD (GOLD 2) and 23 sex-and age-matched healthy smokers underwent a 30 min constant load exercise on 2 occasions separated by 4 weeks. Serum samples were obtained before, 5 min after the start, when the exercise was stopped due to exhaustion (peak) and 20 min after the end of the exercise (rest). Additional control samples were repeatedly taken under fasting conditions 3-7 d after the exercise. In each sample we measured the concentrations of 158 metabolites. We computed the intra-class correlation coefficients (ICC) to assess the reproducibility between visits and the number of metabolites that showed repeatable differences between groups.
RESULTS: Under fasting conditions, none of the serum metabolites was different between groups and following a standardized meal, we found borderline significant group differences only for acylcarnitine C0. Serum taken after 5 min exercise showed significant differences in the level of arginine (Arg), glutamic acid, phosphatidylcholines (PC) diacylC28:1, PCacyl-alkylC30:1, PCacyl-alkylC38:1, hydroxy(OH)-sphingomyelins (SM) C14:1, SMC26:1, the ratio asymmetric dimethyl-arginine (ADMA)/Arg, and the ratio of total OH-SM/total SM (non-OH). At peak exercise the difference observed at 5 min were generally maintained and in addition differences for acylcarnitines C0, sucrose, SMC16.1, SMC22.1, total SM and for the ratios C2/C0, C3/C0, and total acyl-C/C0 were observed. In serum taken after 20 min rest following peak exercise only the differences in arginine and glutamic acid could not be detected anymore, and in addition to the above listed metabolites we found differences between groups for PCacyl-alkylC34:3, PCacyl-alkylC36:2, and the ratio symmetric (S) DMA/Arg. At the same time we found the largest number of metabolites that were reproducible (intra-class correlation coefficients>0.7) in serum taken during and after exercise.
CONCLUSION: Our data suggests that an exercise challenge is capable to amplify COPD biomarker signals, as the number of metabolites showing reproducible differences between groups increased. In addition, the level of most serum metabolites during and after exercise was more reproducible compared to serum taken at baseline after fasting. Exercise challenge therefore appears to be a valuable approach to find specific COPD biomarkers.