Can Your Breath Diagnose Lung Cancer? The Science Behind Breath Biopsies

Introduction
Lung cancer continues to account for many cancer-caused mortalities globally. Its high morbidity rates are primarily due to diagnosis at an advanced stage because early stages of lung cancer usually come with no symptoms. Chest X-ray, CT scan, PET scans, bronchoscopy, and tissue biopsy are among common techniques employed in the diagnosis of lung cancer. However, while offering clinically vital insights into the condition, the methods have several shortcomings such as invasiveness, expense, long processing times, and limited accessibility. This has fueled efforts towards the development of inexpensive, less invasive, quick methods, which breath biopsy has proved to be an ideal option.
Theory underpinning Breath Biopsy
Breath, like blood, contains various gases, some of which include more than two hundred volatile organic compounds (VOCs). The VOCs originate from metabolized products of different reactions occurring in the body. Subsequently, they circulate in the bloodstream before passing out of the body via exhalation through the lungs. In healthy people, the compounds occur in particular concentrations indicative of the physiological state of health. Breast cancer development affects metabolic activity of body cells and induces an increased production of reactive oxygen species. In other words, the development of malignant diseases is accompanied by biochemical disturbances, which include lipid peroxidation, inflammatory processes, energy metabolism, and others. As a result, VOC levels change significantly compared to healthy people. Analyzing this information allows for identifying particular VOC markers of breast cancer and developing a methodology for diagnosing it using breath biopsy approach.
Main Scientific Findings
The pioneering research in this field, which proved the viability of VOC-based diagnostics of lung cancer, was carried out by Phillips et al. (1999). Scientists showed that some particular VOC compounds found in the breath could distinguish cancer patients from healthy people. Based on these results, further work in this area was carried out, and one of the notable works in which the breath patterns associated with breast cancer were analyzed is that by Bajtarevic et al. (2009). These scientists analyzed the breath of 220 patients suffering from this cancer and 441 healthy participants, using such techniques as PTR-MS and GC-MS. Later research has consistently confirmed these conclusions. A number of VOCs have been discovered by scientists, which can be related to the formation of cancer cells in lungs. Among the molecules associated with lung cancer are alkanes, aldehydes, ketones, benzene derivatives, isoprene compounds, and others. Recently, artificial intelligence and machine learning software has started being used in conjunction with breath analyzers to increase efficiency in pattern recognition and diagnosis. Devices called e-noses, which attempt to emulate a human olfactory system, showed encouraging results in distinguishing cancer patients from other people and patients with respiratory illnesses.
Methods Applied in Breath Testing
Different types of analytical methods can be applied for VOC analysis of exhaled air. GC-MS is regarded as the standard method, due to its high sensitivity and the possibility of determining specific chemicals. PTR-MS is another method that allows real-time monitoring without sample preprocessing. SIFT-MS and e-nose technologies are also increasingly used due to their speed of operation. Recently, breath analyzers have become portable, thanks to recent advances in sensor technology. This innovation may prove useful in conducting widespread screening campaigns.
Advantages and Disadvantages
There are many advantages of breath biopsy technique. First, this method is entirely non-invasive and harmless, and the patient will not be exposed to any kind of radiation. The sampling process is easy to perform and can be performed regularly, without causing any pain to patients. It is a relatively quick test which makes it ideal for screening or monitoring. However, there are also some difficulties that should be taken into consideration. Different factors such as smoking habit, diet, medication, age, environment, and existing respiratory problems can have an impact on the breath profile. Furthermore, different methods used for breath sample collection and analysis can result in non-reproducible results from different studies. Another problem is the lack of specificity of most identified volatile organic compounds which could indicate other conditions than cancer.
Future Prospects
The prospects for the future development of breath biopsy technology look very promising. Further advances in the field of nanotechnologies, biosensors, metabolomics, and artificial intelligence could contribute to improvements in the sensitivity and specificity of breath diagnostics. Scientists are currently trying to discover whether breath biopsy is able to provide more information about patients, such as identification of tumor subtypes, assessment of therapeutic effects, and prediction of disease recurrence.
Conclusion
Breath biopsy is considered to be among the most advanced technologies in contemporary pulmonology and cancer diagnostics. Through the analysis of volatile organic compounds in the breath samples, scientists have the ability to diagnose lung cancer non-invasively through metabolic changes. Even though there are several major obstacles for implementation that still need to be overcome, scientific research proves the feasibility of this technology in early diagnosis and screening of lung cancer.
References
Phillips, M., Gleeson, K., Hughes, J. M., Greenberg, J., Cataneo, R. N., Baker, L., & McVay, W. P. (1999). Volatile organic compounds in breath as markers of lung cancer: A cross-sectional study. The Lancet, 353(9168), 1930–1933. https://doi.org/10.1016/S0140-6736(98)07552-7
Bajtarevic, A., Ager, C., Pienz, M., Klieber, M., Schwarz, K., Ligor, M., et al. (2009). Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer, 9, 348. https://doi.org/10.1186/1471-2407-9-348