Noninvasive detection of lung cancer using exhaled breath

Abstract

Early detection of lung cancer is a key factor for increasing the survival rates of lung cancer patients. The analysis of exhaled breath is promising as a noninvasive diagnostic tool for diagnosis of lung cancer. We demonstrate the quantitative analysis of carbonyl volatile organic compounds (VOCs) and identification of lung cancer VOC markers in exhaled breath using unique silicon microreactor technology. The microreactor consists of thousands of micropillars coated with an ammonium aminooxy salt for capture of carbonyl VOCs in exhaled breath by means of oximation reactions. Captured aminooxy-VOC adducts are analyzed by nanoelectrospray Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometry (MS). The concentrations of 2-butanone, 2-hydroxyacetaldehyde, 3-hydroxy-2-butanone, and 4-hydroxyhexenal (4-HHE) in the exhaled breath of lung cancer patients (n = 97) were significantly higher than in the exhaled breath of healthy smoker and nonsmoker controls (n = 88) and patients with benign pulmonary nodules (n = 32). The concentration of 2-butanone in exhaled breath of patients (n = 51) with stages II though IV non–small cell lung cancer (NSCLC) was significantly higher than in exhaled breath of patients with stage I (n = 34). The carbonyl VOC profile in exhaled breath determined using this new silicon microreactor technology provides for the noninvasive detection of lung cancer.

Breath carbonyl compounds as biomarkers of lung cancer

“…Additional advantages of the current study include benchmarking of the simpler models with established statistical / machine-learning methods and optimization of cut-points for both individual VOCs and the number of elevated VOCs for determining whether a patient has lung cancer. It should also be noted that the carbonyl VOCs were equally effective in separating lung cancer cases from both smoking and non-smoking controls, in agreement with what we previously observed [24][25]. A limitation of the current work is that we selected the six VOCs for our simple model based on the best performing classifiers in the test data.…”

“…Our previous work identified four lung cancer markers C 4 H 8 O, 4-HHE, C 4 H 8 O 2 , and C 2 H 4 O 2 [24] and a diagnostic method based on counting the number of elevated these four markers was developed [25]. In this study, two additional markers 4-HNE and C 5 H 10 O were identified by the statistical classification models.…”

“…We have developed a technique utilizing quaternary aminooxy-coated silicon microreactors for selective capture and quantification of these ketones and aldehydes in air [21][22][23] and exhaled breath [24][25]. In this present work, a variety of statistical classification models were used to analyze how the measured concentrations of carbonyl compounds can be used to determine which compounds and models best differentiate between the patient sub-populations.…”

From diagnosis to therapy in lung cancer: management of CT detected pulmonary nodules, a summary of the 2015 Chinese-German Lung Cancer Expert Panel

“…The concentration of 2-butanone in exhaled breath of patients (n=51) with stages II though IV NSCLC was significantly higher than in exhaled breath of patients with stage I (n=34). The carbonyl and volatile organic compounds profile in exhaled breath determined using this new silicon microreactor technology provides for the noninvasive detection of lung cancer (8,9). Exhaled breath analysis in lung cancer patients reaches in small to midsized discovery trials sensitivities and specificities up to ≥90%.…”

Chemoselective reagents for derivatization of trace--level volatile carbonyl compounds using a microreactor approach.

“…29,[30][31] For example, the detection of 4-hydroxyhexenal (4HHE) and 4-hydroxy-2-nonenal (HNE) in expired breath has been correlated with lung cancer. 32,33 Lipoperoxidative production of reactive aldehyde species, such as malondialdehyde (MDA), HNE, 4-hydroxy-2-hexenal (HHE), and acrolein, appears to be the source of many of the α,β-unsaturated carbonyl compound markers associated with disease.…”