Non-invasive Exhaled Breath and Skin Analysis to Diagnose Lung Cancer: Study of Age Effect on Diagnostic Accuracy

[Image: see text] Development of simple, fast, and non-invasive tests for lung cancer diagnostics is essential for clinical practice. In this paper, exhaled breath and skin were studied as potential objects to diagnose lung cancer. The influence of age on the performance of diagnostic models was studied. Gas chromatography in combination with mass spectrometry (MS) was used to analyze the exhaled breath of 110 lung cancer patients and 212 healthy individuals of various ages. Peak area ratios of volatile organic compounds (VOCs) were used for data analysis instead of VOC peak areas. Various machine learning algorithms were applied to create diagnostic models, and their performance was compared. The best results on the test data set were achieved using artificial neural networks (ANNs): classification of patients with lung cancer and young healthy volunteers: 88 ± 4% sensitivity and 83 ± 3% specificity; classification of patients with lung cancer and old healthy individuals: 81 ± 3% sensitivity and 85 ± 1% specificity. The difference between performance of models based on young and old healthy groups was minor. The results obtained have shown that metabolic dysregulation driven by the disease biology is too high, which significantly overlaps the age effect. The influence of tumor localization and histological type on exhaled breath samples of lung cancer patients was studied. Statistically significant differences between some parameters in these samples were observed. A possibility of assessing the disease status by skin analysis in the Zakharyin-Ged zones using an electronic nose based on the quartz crystal microbalance sensor system was evaluated. Diagnostic models created using ANNs allow us to classify the skin composition of patients with lung cancer and healthy subjects of different ages with a sensitivity of 69 ± 2% and a specificity of 68 ± 8% for the young healthy group and a sensitivity of 74 ± 7% and a specificity of 66 ± 6% for the old healthy group. Primary results of skin analysis in the Zakharyin-Ged zones for the lung cancer diagnosis have shown its utility, but further investigation is required to confirm the results obtained.