Collection methods of exhaled volatile organic compounds for lung cancer screening and diagnosis: a systematic review

Background: The identification of volatile organic compounds (VOCs) in exhaled breath has garnered significant research attention as a means of screening and diagnosing lung cancer in recent decades. However, there is no universally accepted protocol for the collection of breath samples to measure VOCs in the clinical context. The purpose of this study was to summarize the current sampling techniques used to obtain VOCs from exhaled breath specifically in the context of lung cancer screening and diagnosis.

Methods: We searched four major literature databases (PubMed, Embase, Web of Science, and The Cochrane Library) to identify studies published from January 1985 to October 2023. Trials that analyzed endogenous VOCs within exhaled breath to screen or diagnose lung cancer were included. The methods used for exhaled breath collection were divided under the following headings: before collection (patient preparation, environmental preparation, contamination detection), during collection (time of breath collection, type of container, breath fraction selected, the volume and route of breath), and after collection (storage of breath samples, VOCs stability).

Results: A total of 89 studies involving 6,409 individuals diagnosed with lung cancer were selected. The methods used to collect the breath varied substantially among the studies. A separate room was prepared for breath collection in 29 studies, the physiological state of the participants was described in 57 studies, and environmental considerations were reported in 41 studies. Polymer bags, specifically Tedlar bags, were the predominant choice for breath sample collection and were used in 58 out of the 89 studies. Alveolar breath was the most commonly selected breath fraction, which was used in 43 studies. Only 15 studies reported the storage conditions of the breath samples, which ranged from -40 ℃ to room temperature, and the stability of VOCs was recorded in 41 studies.

Conclusions: There is an urgent need for breath collection methods to be standardized to maximize the potential of this diagnostic approach. The summarized exhaled breath collection process proposed in this study based on included studies may serve as a method for future clinical research.