Abstract
Background: Aircrew fatigue is a major contributor of operational errors in civil and military aviation, which translates a comprehensive performance associated with both neuromuscular and cognitive states. Here we have used untargeted and non-invasive urinary metabolomics to explore flight fatigue-related aberrations. In this sense, we aimed to identify biomarkers that could better monitor pilot fatigue and also assess its severity to prevent ‘nonfunctional over-reached’ state, thus promoting flight safety. Methods: In this study, 22 active-duty male pilots, who conducted different flight hour duties, were recruited to mimic different levels of fatigue. For this, respective urine samples were collected, before and after flight, and analyzed by liquid chromatography/mass spectrometry (LC/MS). Results: Except for the fatty acids and some amino acids, significant changes on metabolite levels were observed during the progression of flight fatigue. Most of these metabolites corresponded to acyl carnitines, carbohydrates, purines and indoles. The majority of amino acids were downregulated after the flight mission. A total of 61 metabolites were found to be significantly changed along with the extent of flight fatigue. To efficiently discriminate the occurrence of flight fatigue, three candidate biomarkers (beta-guanidinopropionic acid, 3-dehydro-L-gulonate and 2-propylpent-3-enoic acid) were further characterized. Lastly, Bayes discriminant function models were established to stratify pilots with severity of fatigue and, therefore, to aid in flight risk management.Conclusion: To our knowledge, this study inaugurally provides a metabolic profiling in response to flight fatigue, thus offering a novel and effective way to monitor and manage this physiological condition.