title: High sensitivity for lung cancer detection using analysis of exhaled carbonyl compounds.
abstract: OBJECTIVE
  Several volatile carbonyl compounds in exhaled breath have been identified as cancer-specific markers. The potential for these markers to serve as a screening test for lung cancer is reported.
  
  
  METHODS
  Patients with computed tomography-detected intrathoracic lesions and healthy control participants were enrolled from 2011 onward. One liter of breath was collected from a single exhalation from each participant. The contents were evacuated over a silicon microchip, captured by oximation reaction, and analyzed by mass spectrometry. Concentrations of 2-butanone, 3-hydroxy-2-butanone, 2-hydroxyacetaldehyde, and 4-hydroxyhexanal were measured. The overall population was divided into 3 groups: those with lung cancer, benign disease, and healthy controls. An elevated cancer marker was defined as ≥1.5 SDs above the mean concentration of the control population. One or more elevated cancer markers constituted a positive breath test.
  
  
  RESULTS
  In all, 156 subjects had lung cancer, 65 had benign disease, and 194 were healthy controls. A total of 103 (66.0%) lung cancer patients were early stage (stage 0, I, and II). For ≥1 elevated cancer marker, breath analysis showed a sensitivity of 93.6%, and a specificity of 85.6% for lung cancer patients. Additionally, 83.7% of stage I tumors ≤2 cm were detected; whereas only 14% of the control population tested positive. In a comparison of cancer to benign disease, specificity was proportional to the number of elevated cancer markers present.
  
  
  CONCLUSIONS
  Screening using a low-dose CT scan is associated with high cost, repeated radiation exposure, and low accrual. The high sensitivity, convenience, and low cost of breath analysis for carbonyl cancer markers suggests that it has the potential to become a primary screening modality for lung cancer.
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, Louisville, Ky.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Schumer
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, Louisville, Ky.
authors.forename: Jaimin R
authors.initials: JR
authors.lastname: Trivedi
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, Louisville, Ky.
authors.forename: Victor
authors.initials: V
authors.lastname: van Berkel
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, Louisville, Ky.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Black
authors.affiliation: Department of Chemical Engineering, University of Louisville School of Medicine, Louisville, Ky.
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Chemical Engineering, University of Louisville School of Medicine, Louisville, Ky.
authors.forename: Xiao-An
authors.initials: XA
authors.lastname: Fu
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, Louisville, Ky. Electronic address: michael.bousamra@louisville.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Bousamra
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000032:analysis; D000093:Acetoin / Q000032:analysis; D000368:Aged; D000447:Aldehydes / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D001944:Breath Tests; D002074:Butanones / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis*; D008297:Male; D008403:Mass Screening / Q000379:methods*; D013058:Mass Spectrometry; D008875:Middle Aged; D012680:Sensitivity and Specificity; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D000447:Aldehydes; D014408:Biomarkers, Tumor; D002074:Butanones; D055549:Volatile Organic Compounds; C064453:4-hydroxyhexanal; C005222:methylethyl ketone; D000093:Acetoin; D000079:Acetaldehyde; C010972:glycolaldehyde
keywords: breath analysis; lung cancer