Chromatography Profiling of Exhaled Breath VOC Biomarkers for Non-Invasive Asthma Monitoring

There has been growing interest in the identification novel, non-invasive biomarkers reflecting endogenous inflammatory processes in asthma. Agroup of researchersfrom eight hospitals in Spainanalyzed five volatile organic compounds (VOCs) (hexanal, heptanal, nonanal, propanoic acid, and nonanoic acid) that have been previously characterized in patients with controlled asthma, as well as assessed the influence of tobacco exposure on their expression and explore their potential utility in asthma monitoring and therapeutic decision making. Breath samples in this study were analyzed using gas chromatography-mass spectrometry (GC-MS).A paper based on this research was published in ERJ Open Research (1).

The second most prevalent chronic respiratory disease worldwide, asthma is primarily characterized by a chronic inflammation of the airways (2).

VOCs in exhaled breath reflect metabolic activity at the cellular and tissue levels and are closely linked to airway inflammation processes (3,4). VOCs have been investigated in a variety of respiratory conditions, including cystic fibrosis, chronic obstructive pulmonary disease (COPD), and lung cancer, as well as asthma (5-9). For astham, VOC analysis has demonstrated potential for diagnosis, phenotypic and endotype classification, prediction of exacerbations, assessment of adherence, therapeutic guidance, and monitoring of treatment response (10-12).

For this research, exhaled breath samples from 120 clinically controlled asthma patients and 89 healthy controls were collected using BioVOC breath samplers. Samples were analyzed by GC-MS, and hexanal, heptanal, nonanal, propanoic acid, and nonanoic acid were assessed.Compared to healthy controls, asthma patients exhibited a lower frequency of propanoic acid exhalation (25.0% vs53.9%; p<0.001) and higher frequencies of nonanoic acid (30.8% compared with15.7%; p=0.019). These differences continued after adjusting for smoking status. Stratified analysis revealed reduced propanoic acid exhalation in both smoking and non-smoking asthma subgroups compared to their respective controls (21.0% versus 55.6% and 29.3% vs. 51.4%, respectively; p<0.001). Also, asthma in current and former smokers had significantly increased detection of nonanoic acid compared to controls (33.9% vs.11.1%; p=0.0359). Multivariate analysis identified propanoic acid as a protective factor against asthma (OR 0.2 (95% CI 0.1-0.4); p<0.001), whereas nonanoic acid significantly increased asthma risk (OR 4.5 (95% CI 1.8-12.6); p=0.003) (1).

The researchers concluded from their analysis that “exhaled propanoic and nonanoic acids may serve as complementary non-invasive biomarkers for monitoring controlled asthma, independently of tobacco exposure. VOC analysis has promising potential to improve asthma management, therapeutic monitoring and patient stratification.” (1)

However, the researchers recognized that their study had limitations, particularly, as they stated, “due the use of historical controls, which may introduce selection or temporal biases. Furthermore,” they added, “VOCs were analyzed qualitatively rather than quantitatively, which limits the ability to measure absolute concentrations or identify dose–response relationships. The relatively advanced age of the study cohort (mean age 64 years) may limit the external validity of our findings in younger populations with asthma.” (1)

“Despite these limitations,” they concluded, “our study presents important strengths: the rigorous internal and external validation of VOC biomarkers in a reference center, careful controlling for ambient VOC contamination, and a detailed evaluation of tobacco exposure, all of which reinforce the reliability and clinical relevance of our findings.” (1)

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References

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