Critical Review of Volatile Organic Compound Analysis in Breath and In Vitro Cell Culture for Detection of Lung Cancer

Overview

Journal Metabolites

Publisher MDPI

Date 2019 Mar 21

PMID 30889835

Citations 54

Authors

Zhunan Jia

Abhijeet Patra

Viknish Krishnan Kutty

Thirumalai Venkatesan

Affiliations

Soon will be listed here.

Abstract

Breath analysis is a promising technique for lung cancer screening. Despite the rapid development of breathomics in the last four decades, no consistent, robust, and validated volatile organic compound (VOC) signature for lung cancer has been identified. This review summarizes the identified VOC biomarkers from both exhaled breath analysis and in vitro cultured lung cell lines. Both clinical and in vitro studies have produced inconsistent, and even contradictory, results. Methodological issues that lead to these inconsistencies are reviewed and discussed in detail. Recommendations on addressing specific issues for more accurate biomarker studies have also been made.

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References

Phillips M, Gleeson K, Hughes J, Greenberg J, Cataneo R, Baker L . Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet. 1999; 353(9168):1930-3. DOI: 10.1016/S0140-6736(98)07552-7. View

Phillips M, Herrera J, Krishnan S, Zain M, Greenberg J, Cataneo R . Variation in volatile organic compounds in the breath of normal humans. J Chromatogr B Biomed Sci Appl. 1999; 729(1-2):75-88. DOI: 10.1016/s0378-4347(99)00127-9. View

Phillips M, Greenberg J, Cataneo R . Effect of age on the profile of alkanes in normal human breath. Free Radic Res. 2000; 33(1):57-63. DOI: 10.1080/10715760000300611. View

Phillips M, Cataneo R, Greenberg J, Gunawardena R, Naidu A . Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. J Lab Clin Med. 2000; 136(3):243-9. DOI: 10.1067/mlc.2000.108943. View

Smith D, Wang T, Sule-Suso J, Spanel P, El Haj A . Quantification of acetaldehyde released by lung cancer cells in vitro using selected ion flow tube mass spectrometry. Rapid Commun Mass Spectrom. 2003; 17(8):845-50. DOI: 10.1002/rcm.984. View

Phillips M, Cataneo R, Cummin A, Gagliardi A, Gleeson K, Greenberg J . Detection of lung cancer with volatile markers in the breath. Chest. 2003; 123(6):2115-23. DOI: 10.1378/chest.123.6.2115. View

Di Natale C, Macagnano A, Martinelli E, Paolesse R, DArcangelo G, Roscioni C . Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. Biosens Bioelectron. 2003; 18(10):1209-18. DOI: 10.1016/s0956-5663(03)00086-1. View

Machado R, Laskowski D, Deffenderfer O, Burch T, Zheng S, Mazzone P . Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med. 2005; 171(11):1286-91. PMC: 2718462. DOI: 10.1164/rccm.200409-1184OC. View

Poli D, Carbognani P, Corradi M, Goldoni M, Acampa O, Balbi B . Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study. Respir Res. 2005; 6:71. PMC: 1185565. DOI: 10.1186/1465-9921-6-71. View

10.

Schubert J, Miekisch W, Birken T, Geiger K, Noldge-Schomburg G . Impact of inspired substance concentrations on the results of breath analysis in mechanically ventilated patients. Biomarkers. 2005; 10(2-3):138-52. DOI: 10.1080/13547500500050259. View

11.

Lechner M, Moser B, Niederseer D, Karlseder A, Holzknecht B, Fuchs M . Gender and age specific differences in exhaled isoprene levels. Respir Physiol Neurobiol. 2006; 154(3):478-83. DOI: 10.1016/j.resp.2006.01.007. View

12.

Birken T, Schubert J, Miekisch W, Noldge-Schomburg G . A novel visually CO2 controlled alveolar breath sampling technique. Technol Health Care. 2006; 14(6):499-506. View

13.

Larstad M, Toren K, Bake B, Olin A . Determination of ethane, pentane and isoprene in exhaled air--effects of breath-holding, flow rate and purified air. Acta Physiol (Oxf). 2007; 189(1):87-98. DOI: 10.1111/j.1748-1716.2006.01624.x. View

14.

Mazzone P, Hammel J, Dweik R, Na J, Czich C, Laskowski D . Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array. Thorax. 2007; 62(7):565-8. PMC: 2117257. DOI: 10.1136/thx.2006.072892. View

15.

Phillips M, Altorki N, Austin J, Cameron R, Cataneo R, Greenberg J . Prediction of lung cancer using volatile biomarkers in breath. Cancer Biomark. 2007; 3(2):95-109. DOI: 10.3233/cbm-2007-3204. View

16.

Belda-Iniesta C, De Castro Carpeno J, Carrasco J, Moreno V, Casado Saenz E, Feliu J . New screening method for lung cancer by detecting volatile organic compounds in breath. Clin Transl Oncol. 2007; 9(6):364-8. DOI: 10.1007/s12094-007-0068-6. View

17.

Chen X, Xu F, Wang Y, Pan Y, Lu D, Wang P . A study of the volatile organic compounds exhaled by lung cancer cells in vitro for breath diagnosis. Cancer. 2007; 110(4):835-44. DOI: 10.1002/cncr.22844. View

18.

Schulz S, Dickschat J . Bacterial volatiles: the smell of small organisms. Nat Prod Rep. 2007; 24(4):814-42. DOI: 10.1039/b507392h. View

19.

Dragonieri S, Annema J, Schot R, van der Schee M, Spanevello A, Carratu P . An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. Lung Cancer. 2008; 64(2):166-70. DOI: 10.1016/j.lungcan.2008.08.008. View

20.

Filipiak W, Sponring A, Mikoviny T, Ager C, Schubert J, Miekisch W . Release of volatile organic compounds (VOCs) from the lung cancer cell line CALU-1 in vitro. Cancer Cell Int. 2008; 8:17. PMC: 2639533. DOI: 10.1186/1475-2867-8-17. View