Detection of lung cancer with volatile markers in the breath.
OBJECTIVE
To evaluate volatile organic compounds (VOCs) in the breath as tumor markers in lung cancer. Alkanes and monomethylated alkanes are oxidative stress products that are excreted in the breath, the catabolism of which may be accelerated by polymorphic cytochrome p450-mixed oxidase enzymes that are induced in patients with lung cancer.


METHODS
Combined case-control and cross-sectional study.


METHODS
Five academic pulmonary medicine services in the United States and the United Kingdom.


METHODS
One hundred seventy-eight bronchoscopy patients and 41 healthy volunteers.


METHODS
Breath samples were analyzed by gas chromatography and mass spectroscopy to determine alveolar gradients (ie, the abundance in breath minus the abundance in room air) of C4-C20 alkanes and monomethylated alkanes.


METHODS
Patients with primary lung cancer (PLC) were compared to healthy volunteers, and a predictive model was constructed using forward stepwise discriminant analysis of the alveolar gradients. This model was cross-validated with a leave-one-out jackknife technique and was tested in two additional groups of patients who had not been used to develop the model (ie, bronchoscopy patients in whom cancer was not detected, and patients with metastatic lung cancer [MLC]).


RESULTS
Eighty-seven of 178 patients had lung cancer (PLC, 67 patients; MLC, 15 patients; undetermined, 5 patients). A predictive model employing nine VOCs identified PLC with a sensitivity of 89.6% (60 of 67 patients) and a specificity of 82.9% (34 of 41 patients). On cross-validation, the sensitivity was 85.1% (57 of 67 patients) and the specificity was 80.5% (33 of 41 patients). The stratification of patients by tobacco smoking status, histologic type of cancer, and TNM stage of cancer revealed no marked effects. In the two additional tests, the model predicted MLC with a sensitivity of 66.7% (10 of 15 patients), and it classified the cancer-negative bronchoscopy patients with a specificity of 37.4% (34 of 91 patients).


CONCLUSIONS
Compared to healthy volunteers, patients with PLC had abnormal breath test findings that were consistent with the accelerated catabolism of alkanes and monomethylated alkanes. A predictive model employing nine of these VOCs exhibited sufficient sensitivity and specificity to be considered as a screen for lung cancer in a high-risk population such as adult smokers.
Phillips
Michael
M
Menssana Research Inc, Fort Lee, NJ 07024, USA.
Cataneo
Renee N
RN
Cummin
Andrew R C
AR
Gagliardi
Anthony J
AJ
Gleeson
Kevin
K
Greenberg
Joel
J
Maxfield
Roger A
RA
Rom
William N
WN
D000473:Alkanes / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis*; D001944:Breath Tests / Q000379:methods*; D001999:Bronchoscopy; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009930:Organic Chemicals / Q000032:analysis; D012680:Sensitivity and Specificity; D014835:Volatilization
D000473:Alkanes; D014408:Biomarkers, Tumor; D009930:Organic Chemicals