title: Non-invasive breath analysis of pulmonary nodules.
abstract: BACKGROUND
  The search for non-invasive diagnostic methods of lung cancer (LC) has led to new avenues of research, including the exploration of the exhaled breath. Previous studies have shown that LC can, in principle, be detected through exhaled-breath analysis. This study evaluated the potential of exhaled-breath analysis for the distinction of benign and malignant pulmonary nodules (PNs).
  
  
  METHODS
  Breath samples were taken from 72 patients with PNs in a prospective trial. Profiles of volatile organic compounds were determined by (1) gas chromatography/mass spectrometry (GC-MS) combined with solid-phase microextraction and (2) a chemical nanoarray.
  
  
  RESULTS
  Fifty-three PNs were malignant and 19 were benign with similar smoking histories and comorbidities. Nodule size (mean ± SD) was 2.7 ± 1.7 versus 1.6 ± 1.3 cm (p = 0.004), respectively. Within the malignant group, 47 were non-small-cell lung cancer and six were small-cell lung cancer. Thirty patients had early-stage disease and 23 had advanced disease. Gas chromatography/mass spectrometry analysis identified a significantly higher concentration of 1-octene in the breath of LC, and the nanoarray distinguished significantly between benign versus malignant PNs (p < 0.0001; accuracy 88 ± 3%), between adeno- and squamous-cell carcinomas [LINE SEPARATOR](p < 0.0001; 88 ± 3%) and between early stage and advanced disease (p < 0.0001; 88 ± 2%).
  
  
  CONCLUSIONS
  In this pilot study, breath analysis discriminated benign from malignant PNs in a high-risk cohort based on LC-related volatile organic compound profiles. Furthermore, it discriminated adeno- and squamous-cell carcinoma and between early versus advanced disease. Further studies are required to validate this noninvasive approach, using a larger cohort of patients with PNs detected by computed tomography.
authors.affiliation: Thoracic Cancer Research and Detection Center, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Peled
authors.forename: Meggie
authors.initials: M
authors.lastname: Hakim
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
authors.forename: York E
authors.initials: YE
authors.lastname: Miller
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Kennedy
authors.forename: Jane
authors.initials: J
authors.lastname: Mattei
authors.forename: John D
authors.initials: JD
authors.lastname: Mitchell
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.forename: Hossam
authors.initials: H
authors.lastname: Haick
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000368:Aged; D001944:Breath Tests; D018287:Carcinoma, Large Cell / Q000175:diagnosis* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis* / Q000378:metabolism; D052617:Solid Phase Microextraction; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D055549:Volatile Organic Compounds