Exhaled volatile organic compounds associated with risk factors for obstructive pulmonary diseases: a systematic review

BACKGROUND: Asthma and COPD are among the most common respiratory diseases. To improve the early detection of exacerbations and the clinical course of asthma and COPD new biomarkers are needed. The development of noninvasive metabolomics of exhaled air into a point-of-care tool is an appealing option. However, risk factors for obstructive pulmonary diseases can potentially introduce confounding markers due to altered volatile organic compound (VOC) patterns being linked to these risk factors instead of the disease. We conducted a systematic review and presented a comprehensive list of VOCs associated with these risk factors. METHODS: A PRISMA-oriented systematic search was conducted across PubMed, Embase and Cochrane Libraries between 2000 and 2022. Full-length studies evaluating VOCs in exhaled breath were included. A narrative synthesis of the data was conducted, and the Newcastle–Ottawa Scale was used to assess the quality of included studies. RESULTS: The search yielded 2209 records and, based on the inclusion/exclusion criteria, 24 articles were included in the qualitative synthesis. In total, 232 individual VOCs associated with risk factors for obstructive pulmonary diseases were found; 58 compounds were reported more than once and 12 were reported as potential markers of asthma and/or COPD in other studies. Critical appraisal found that the identified studies were methodologically heterogeneous and had a variable risk of bias. CONCLUSION: We identified a series of exhaled VOCs associated with risk factors for asthma and/or COPD. Identification of these VOCs is necessary for the further development of exhaled metabolites-based point-of-care tests in these obstructive pulmonary diseases.