Analysis of exhaled breath with chromatography or electronic nose. Diagnosis of lung cancer by multifactorial logistic regression analysis Dr.med. Māris Bukovskis 1 2 4, Dr.biol. Gunta Strazda 1 2 3, Dr.med Uldis Kopeika 2 5, Dr.biol.Normunds Jurka 2, Līga Balode 2, Dr. Jevgenija Aprinceva 3, Dr. Ainis Pirtnieks 5, Prof. Immanuels Taivans Department of Pulmonology and Allergology, Pauls Stradins Clinical University Hospital, 2 Institute of Experimental and Clinical Medicine, University of Latvia, 3 Faculty of Medicine, University of Latvia, 4 Department of Internal Medicine, Faculty of Medicine, University of Latvia, 5 Department of Thoracic Surgery, Pauls Stradins Clinical University Hospital

Lung cancer mortality and diagnostic methods Lung cancer is the leading cancer killer in both men and women and causes more deaths than the next three most common cancers combined (colon, breast and prostate)Lung cancer is the leading cancer killer in both men and women and causes more deaths than the next three most common cancers combined (colon, breast and prostate) % of stage I lung cancer patients suvive 5- years compared to % of patients with stage III lung cancer % of stage I lung cancer patients suvive 5- years compared to % of patients with stage III lung cancer Available diagnostic methods - nonsensitive (sputum, chest x-ray), expensive (CT) or invasive (FB)Available diagnostic methods - nonsensitive (sputum, chest x-ray), expensive (CT) or invasive (FB) Goldstraw P et al. J Thorac Oncol 2007 American Cancer Society Cancer. Facts and Figures 2012

VOC’s in exhaled breath Lung cancer sniffer dogs CBC News Aug 17, 2011 Gordon SM et al. Clin Chem 1985 Machado et al. AJRCCM 2005 Chen X et al. Cancer 2007

Is this so easy?

Complex consisting of desorbtion unit, gas chromatograph and mass spectrometer

Chromatogram showing multiple peaks representing particular chemical substances

Time (s) Relative electric resistance Baseline Response of 32 sensors to air sample Functional principles of electronic nose ΔR max Cyranose 320

Methods 475 patients in total, 252 of them lung cancer patients, and 223 patients with different lung diseases and healthy volunteers, were recruitedin the study 475 patients in total, 252 of them lung cancer patients, and 223 patients with different lung diseases and healthy volunteers, were recruitedin the study Collection and sampling of exhaled air by electronic nose (Cyranose320) Collection and sampling of exhaled air by electronic nose (Cyranose320) Analysis of “smell prints” by multifactorial regression analysis Analysis of “smell prints” by multifactorial regression analysis

Results Classification of cases in nonsmokers Lung cancer No cancer Lung cancer PPV 91.4% No cancer 5120 NPV 96.0% Sensitivity 96.2% Specificity 90.6% Classification of cases in smokers Lung cancer No cancer Lung cancer 1147 PPV 94.2% No cancer 584 NPV 94.4% Sensitivity 95.8% Specificity 92.3%

Why is this so valuable? Advantages of exhaled breath analysis by electronic nose: Advantages of exhaled breath analysis by electronic nose: - cheap - cheap - easy to do - easy to do - non-invasive - non-invasive - sufficiently accurate - sufficiently accurate - possible to do in a large number of patients at risk (all smokers > 50 years of age) - possible to do in a large number of patients at risk (all smokers > 50 years of age) Chromatography analysis is valuable for scientific research purposes Chromatography analysis is valuable for scientific research purposes

Thank You for Your Attention! How to sniff out the disease?