Volatile Organic Compound Analysis in Pediatric Asthma: A New Clinical Tool

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Volatile organic compound analysis demonstrated moderate to good prediction accuracy in pediatric patients with asthma.
Volatile organic compound analysis demonstrated moderate to good prediction accuracy in pediatric patients with asthma.

An estimated 6.2 million children in the United States have asthma, comprising 8.4% of the population younger than 18 years.1 While asthma control in pediatric patients has improved in recent years, diagnosis remains particularly challenging in preschool children due to the lack of tools that can differentiate between asthma and asthma-like symptoms.

“In addition, clinical objectives such as the assessment of asthma severity and the prediction of treatment response and risk for exacerbations, are still challenging with current available methods” wrote the authors of a review published in December 2017 in Pediatric Pulmonology.2 “To optimize asthma diagnosis and treatment, the identification of clinically relevant asthma phenotypes would be valuable, but existing clinical markers cannot successfully distinguish different phenotypes.”

The metabolomic analysis of exhaled air is referred to as “breathomics,” which would be especially valuable for use in pediatric patients because it is noninvasive and easy to administer. Human exhaled breath contains thousands of volatile organic compounds (VOCs), including ethanol, isoprene, benzene, and acetone, that could potentially be used in asthma diagnosis and phenotyping. In addition, the “noninvasive and quick profiling of patients through an exhaled-VOC based tool might help us to predict a pulmonary exacerbation,” review coauthor Paul Brinkman, MSc, a biomedical engineer at the Academic Medical Centre of the University of Amsterdam in The Netherlands, told Pulmonology Advisor.

Exogenous VOCs originate from the environment, while endogenous VOCs result from internal metabolic processes. “[T]hese endogenous compounds are [especially] interesting for the development of diagnostic tools since they originate from either the conducting airways and alveoli, or the circulation that transfers the compounds from elsewhere in the body to the lungs,” as explained in the review. Previous findings show preliminary support for the use of breathomics in asthma diagnosis and phenotyping in adults.3,4

The current review examined 12 studies from the past 10 years — from 2010 to 2017 — that explored the use of VOC analysis in pediatric patients. All but 2 studies used gas chromatography-mass spectrometry to analyze VOCs. Electronic nose (eNose) technology was used to analyze VOCs in wheezing children vs asymptomatic children, either with or without rhinovirus infection, and laser-based spectroscopy was used to distinguish children with asthma from healthy children and children with cystic fibrosis.

Overall, the results demonstrated that VOC analysis can discriminate between children with and without asthma, and between asthma and transient wheezing in preschool children. VOC analysis was also shown to predict asthma exacerbations with a good level of accuracy, ranging from 80% to 100%. Sensitivity and specificity ranged from 79% to 98% and 50% to 100%, respectively.

However, several challenges must be addressed before this approach can be reliably used in clinical practice. These include potential confounding factors that can influence the compounds in exhaled breath, such as diet, exercise, smoking, and compounds in ambient air as well as the lack of standardized collection, storage, and analysis techniques across the breath analysis field, and the lack of external validation in independent cohorts.

Overall, the studies reviewed “show moderate to good prediction accuracy, thereby qualifying breathomics for future application in early asthma diagnosis,” the researchers concluded. “Such a noninvasive tool may be the next step toward stratified and personalized medicine in respiratory pediatric disease.”

According to Mr. Brinkman, further research in the field of breathomics should focus on standardization of methods, independent validation of outcomes, performance of randomized controlled trials, pathophysiological pathways, and eNose sensor development.

References

  1. US Centers for Disease Control and Prevention (CDC). National Center for Health Statistics. Asthma. Last updated March 31, 2017. https://www.cdc.gov/nchs/fastats/asthma.htm. Accessed January 12, 2018.
  2. Neerincx AH, Vijverberg SJH, Bos LDJ, et al. Breathomics from exhaled volatile organic compounds in pediatric asthma. Pediatr Pulmonol. 2017;52(12):1616-1627.
  3. Bos LD, Sterk PJ, Fowler SJ. Breathomics in the setting of asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016;138(4):970-976.
  4. van der Schee MP, Paff T, Brinkman P, van Aalderen WMC, Haarman EG, Sterk PJ. Breathomics in lung disease. Chest. 2015;147(1):224-231.

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