Quantitative analysis of exhaled carbonyl compounds distinguishes benign from malignant pulmonary disease

Objectives: The analysis of exhaled breath is a promising noninvasive tool for the diagnosis of lung cancer, but its clinical relevance has yet to be established. We report the analysis of exhaled volatile carbonyl compounds for the identification of specific carbonyl cancer markers to differentiate benign pulmonary disease from early-stage lung cancer and to compare its diagnostic accuracy with positron emission tomography (PET) scans. Methods: Aminooxy-coated silicon microchips were used for the selective capture of exhaled carbonyls by an oximation reaction. Breath samples were collected then directed through the silicon chips by applying a vacuum. Carbonyl adducts were analyzed by Fourier transform mass spectrometry. Eighty-eight control subjects, 107 patients with lung cancer (64 stage 0, I, or II), 40 patients with benign pulmonary disease, and 7 patients with a solitary pulmonary metastasis participated. Analysis of cancer markers was performed blinded to the pathologic results. Results: Four carbonyls were defined as cancer markers with significantly higher concentrations in patients with lung cancer. The number of increased cancer markers distinguished benign disease from both early and stage III and IV lung cancer. For early-stage disease, defining greater than 2 increased markers as diagnostic of lung cancer resulted in 83% sensitivity and 74% specificity. PET scans for this same cohort resulted in 90% sensitivity but only 39% specificity. Markers normalized for 3 of the 4 markers after resection of the lung cancer. Conclusions: Analysis of specific exhaled carbonyls can differentiate early lung cancer from benign pulmonary disease. Breath analysis was more specific than PET for a lung cancer diagnosis. Judicious use of these data may expedite the care of patients with lung cancer.