title: Exhaled breath analysis with a colorimetric sensor array for the identification and characterization of lung cancer.
abstract: BACKGROUND
  The pattern of exhaled breath volatile organic compounds represents a metabolic biosignature with the potential to identify and characterize lung cancer. Breath biosignature-based classification of homogeneous subgroups of lung cancer may be more accurate than a global breath signature. Combining breath biosignatures with clinical risk factors may improve the accuracy of the signature.
  
  
  OBJECTIVE
  To develop an exhaled breath biosignature of lung cancer using a colorimetric sensor array and to determine the accuracy of breath biosignatures of lung cancer characteristics with and without the inclusion of clinical risk factors.
  
  
  METHODS
  The exhaled breath of 229 study subjects, 92 with lung cancer and 137 controls, was drawn across a colorimetric sensor array. Logistic prediction models were developed and statistically validated based on the color changes of the sensor. Age, sex, smoking history, and chronic obstructive pulmonary disease were incorporated in the prediction models.
  
  
  RESULTS
  The validated prediction model of the combined breath and clinical biosignature was moderately accurate at distinguishing lung cancer from control subjects (C-statistic 0.811). The accuracy improved when the model focused on only one histology (C-statistic 0.825-0.890). Individuals with different histologies could be accurately distinguished from one another (C-statistic 0.864 for adenocarcinoma versus squamous cell carcinoma). Moderate accuracies were noted for validated breath biosignatures of stage and survival (C-statistic 0.785 and 0.693, respectively).
  
  
  CONCLUSIONS
  A colorimetric sensor array is capable of identifying exhaled breath biosignatures of lung cancer. The accuracy of breath biosignatures can be optimized by evaluating specific histologies and incorporating clinical risk factors.
authors.affiliation: Respiratory Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. mazzonp@ccf.org
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mazzone
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Yaomin
authors.initials: Y
authors.lastname: Xu
authors.forename: Tarek
authors.initials: T
authors.lastname: Mekhail
authors.forename: Mary C
authors.initials: MC
authors.lastname: Beukemann
authors.forename: Jie
authors.initials: J
authors.lastname: Na
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Kemling
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Suslick
authors.forename: Madhu
authors.initials: M
authors.lastname: Sasidhar
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D000328:Adult; D000368:Aged; D001944:Breath Tests; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000175:diagnosis* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology; D003124:Colorimetry; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve
references.citation: Nat Chem. 2009 Oct;1(7):562-7
references.pmid: 20160982
references.citation: Nano Lett. 2008 Nov;8(11):3631-5
references.pmid: 18839997
references.citation: J Appl Physiol (1985). 2004 Apr;96(4):1371-9
references.pmid: 14672964
references.citation: Cancer Biomark. 2007;3(2):95-109
references.pmid: 17522431
references.citation: Cancer. 2007 Aug 15;110(4):835-44
references.pmid: 17599760
references.citation: Cancer Res. 1996 Aug 15;56(16):3725-30
references.pmid: 8706015
references.citation: Lung Cancer. 2008 Mar;59(3):340-9
references.pmid: 17920722
references.citation: Cancer Res. 2001 Dec 1;61(23):8578-85
references.pmid: 11731445
references.citation: Thorax. 2007 Jul;62(7):565-8
references.pmid: 17327260
references.citation: Lung Cancer. 2010 Feb;67(2):227-31
references.pmid: 19409642
references.citation: Anal Chem. 2006 Jun 1;78(11):3591-600
references.pmid: 16737212
references.citation: Cancer Prev Res (Phila). 2010 May;3(5):664-9
references.pmid: 20424129
references.citation: Thorax. 2009 Sep;64(9):737-8
references.pmid: 19717705
references.citation: Thorax. 2009 Sep;64(9):744-8
references.pmid: 19158121
references.citation: J Clin Oncol. 2008 Feb 20;26(6):983-94
references.pmid: 18281673
references.citation: Am J Respir Crit Care Med. 2005 Jun 1;171(11):1286-91
references.pmid: 15750044
references.citation: Nat Nanotechnol. 2009 Oct;4(10):669-73
references.pmid: 19809459
references.citation: J Chromatogr A. 2009 Apr 3;1216(14):2749-56
references.pmid: 19036381
references.citation: J Allergy Clin Immunol. 2007 Oct;120(4):856-62
references.pmid: 17658592
references.citation: Anal Chem. 2010 Nov 15;82(22):9433-40
references.pmid: 20954720
references.citation: Proc Natl Acad Sci U S A. 1971 Oct;68(10):2374-6
references.pmid: 5289873
references.citation: Anal Chem. 2010 Mar 1;82(5):2067-73
references.pmid: 20143838
references.citation: Acta Biomed. 2008;79 Suppl 1:64-72
references.pmid: 18924311
references.citation: Anticancer Res. 2009 Jan;29(1):419-26
references.pmid: 19331181
references.citation: Lung Cancer. 2010 Apr;68(1):44-50
references.pmid: 19559498
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):182-95
references.pmid: 20056637
references.citation: J Clin Oncol. 2008 Jul 20;26(21):3543-51
references.pmid: 18506025
references.citation: J Proteome Res. 2010 Aug 6;9(8):4071-81
references.pmid: 20560663
references.citation: J Breath Res. 2008 Jun;2(2):026007
references.pmid: 21383448
references.citation: Lung Cancer. 2009 May;64(2):166-70
references.pmid: 18834643
references.citation: BMC Cancer. 2009 Sep 29;9:348
references.pmid: 19788722
references.citation: Biosens Bioelectron. 2003 Sep;18(10):1209-18
references.pmid: 12835038
references.citation: Mol Cell Biol. 2006 Jul;26(14):5336-47
references.pmid: 16809770
references.citation: Virchows Arch. 2010 Dec;457(6):715-25
references.pmid: 20941505
references.citation: MRS Bull. 2004 Oct;29(10):720-5
references.pmid: 15991401
references.citation: Cancer Cell Int. 2008 Nov 24;8:17
references.pmid: 19025629
references.citation: Clin Chem Lab Med. 2009;47(5):550-60
references.pmid: 19397483