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.

Highlights

  • Cancer is the second leading cause of death by disease worldwide, exceeded only by heart disease [1]

  • The pioneering study on volatile organic compound (VOC) in exhaled breath from lung cancer patients was done by Gordon et al in 1985 using gas chromatography mass spectrometry (GC-MS) [21]

  • Some studies required subjects to fast for 12 h, or overnight, before breath collection [25,42,45,47], while other studies had no restrictions; It is not understood how long it takes for the VOCs from diet to be eliminated from breath

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Summary

Introduction

Cancer is the second leading cause of death by disease worldwide, exceeded only by heart disease [1]. In the last few decades, extensive effort has been focused on searching for VOC biomarkers for lung cancer, either from the headspace of lung cancer cells or from the exhaled breath of patients Both clinical and in vitro studies have failed to produce a consistent and validated list. This review aims to summarize the volatile markers produced by these studies in the last 30 years and discuss the methodological issues that have led to the inconsistencies between different studies. Zhou et al discussed the recent developments in the analytical techniques of breath analysis for lung cancer detection [20]. None of these reviews discussed in vitro studies or evaluated the methodological issues of these studies

VOC Biomarkers of Lung Cancer in Exhaled Breath
Volatile
12. Disease Stage
Phase of Breath Sample Collected
Temperature and Humidity of Environmental Air
Contamination from Collection Systems
Smoking
2.10. Comorbidity
2.11. Disease Staging
2.12. Histology
In Vitro Studies
Findings
Conclusions
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