Differentiating benign and malignant solitary pulmonary nodules through exhaled breath analysis.

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide, with early detection significantly improving survival. Lung nodules are a common finding, both as incidental solitary pulmonary nodules (SPNs) and in lung cancer screening programmes. Accurately distinguishing benign from malignant nodules, particularly small ones, remains challenging. Determining which nodules require further investigation is crucial for optimising early lung cancer detection and reducing unnecessary procedures. Therefore, volatile organic compounds (VOCs) in exhaled breath are analysed using multicapillary column/ion mobility spectrometry (MCC/IMS) to differentiate malignant from benign SPNs, serving as potential biomarkers for lung cancer. Methods: A total of 65 patients with an incidental, solitary pulmonary malignant (n=41) or benign (n=24) nodule were prospectively included. Two models were developed: a pre-computed tomography (CT) scan situation for triaging high-risk individuals prior to imaging, and a post-CT scan situation to assist with nodule management and follow-up. Results: Four VOCs (VOC37, VOC46, VOC58 and VOC128) were identified as key compounds, showing strong diagnostic performance (area under the curve 0.900 for pre-CT scan and 0.897 for post-CT scan). Conclusions: Our findings suggest that breath analysis could improve nodule management by refining patient selection for CT screening and reducing unnecessary invasive procedures or follow-up scans. Further validation through larger multicentre studies is needed to confirm these results.