Investigation of gender-specific exhaled breath volatome in humans by GCxGC-TOF-MS.

Exploring gender-specific metabolic differences in biofluids provides a basic understanding of the physiological and metabolic phenotype of healthy subjects. Many reports have shown gender-specific metabolome profiles in the urine and serum of healthy subjects; however, limited studies focusing on exhaled human breath are available in the literature. In this study, we profiled the exhaled breath (similar to 450 mL) volatile organic compounds (VOCs) of 47 healthy volunteers (age: 19-47; 23 male (M) and 24 female (F)) using a multidimensional gas chromatography and mass spectrometry and employed chemometric analysis to identify gender-specific VOCs. Eleven exhaled breath VOCs were identified from both uni and multivariate analysis from a training set (M = 15, F = 15) that could differentiate the genders within a healthy population. A partial least-squares discriminate analysis (PLS-DA) model built using these putative markers showed high accuracy in predicting (area under the receiver operating characteristic curve >0.9) a hold out/test sample set (n = 17). The outcomes of this report open up new avenues to undertake larger studies to elucidate the association of exhaled breath metabolites with gender-specific disease phenotypes and pharmacokinetics in the future.