One Blow To Obtain Integrated Information on Metals, NO, and Metabolites in Breath Gas by Mass Spectrometry

Human exhaled breath carries multidimensional chemical information that reflects dynamic metabolic processes, yet conventional analyses remain fragmented, targeting volatile metabolites while overlooking inorganic components. Herein, a mass spectrometry-based platform has been established to quantitatively obtain integrated rich information on metals, nitric oxide (NO), and metabolites derived from a single exhaled breath sample. For improved diagnosis, 33 exhaled metabolites, 14 metal species, and trace NO from 51 healthy volunteers and 90 lung cancer (LC) patients were successfully identified using the exhaled breath sample sets collected from the volunteers. The integrated analysis reveals disease-specific chemical linkages, with increased Na, Ca, Al and reduced Mn, Cr, Mo in LC patient breath samples. These elemental alterations correlate strongly with fluctuations in NO and metabolites such as glutaminylcysteine. Results from individual and integrated analyses demonstrate that metal dysregulation reshapes NO-mediated redox balance and alters lipid and amino acid metabolism. For LC diagnosis, integrated metal ion, NO, and metabolite data enable higher accuracy, with AUCs >0.99. Consequently, the one-blow accounting three-dimension strategy sheds light on a more comprehensive picture of life metabolism by simultaneously obtaining integrated information on metals, NO, and metabolites with mass spectrometry, providing a novel platform for advanced applications in life science, clinical diagnosis, and therapy evaluation.