Exhaled volatile organic compounds as markers for medication use in asthma. Issue 2 (27th February 2020)

• Record Type: Journal Article
• Authors: Brinkman, Paul; Ahmed, Waqar M.; Gómez, Cristina; Knobel, Hugo H.; Weda, Hans; Vink, Teunis J.; Nijsen, Tamara M.; Wheelock, Craig E.; Dahlen, Sven-Erik; Montuschi, Paolo; Knowles, Richard G.; Vijverberg, Susanne J.; Maitland-van der Zee, Anke H.; Sterk, Peter J.; Fowler, Stephen J.
• Is Part Of: European respiratory journal. Volume 55:Issue 2(2020)
• Publication Date: 2020-02-27
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.00544-2019
• Languages: English
• ISSNs: 0903-1936

Abstract

Introduction: Asthma is a heterogeneous condition, characterised by chronic inflammation of the airways, typically managed with inhaled bronchodilators and corticosteroids. In the case of uncontrolled asthma, oral corticosteroids (OCSs) are often prescribed. Good adherence and inhalation technique are associated with improved outcomes; however, it is difficult to monitor appropriate drug intake and effectiveness in individual patients. Exhaled breath contains thousands of volatile organic compounds (VOCs) that reflect changes in the body's chemistry and may be useful for monitoring drug pharmacokinetics/pharmacodynamics. We aimed to investigate the association of exhaled VOCs in severe asthma patients from the U-BIOPRED cohort (by gas chromatography coupled with time-of-flight mass spectrometry) with urinary levels of salbutamol and OCSs (by liquid chromatography coupled with high-resolution mass spectrometry). Methods: Samples were collected at baseline and after 12–18 months of follow-up. Statistical analysis was based on univariate and multivariate modelling, followed by area under the receiver operating characteristic curve (AUC) calculation. Results were verified through longitudinal replication and independent validation. Results: Data were available for 78 patients (baseline n=48, replication n=30 and validation n=30). Baseline AUC values were 82.1% (95% CI 70.4–93.9%) for salbutamol and 78.8% (95% CI 65.8–91.8%) for OCS. These outcomes could be adequately replicated and validated. Additional regression analysis between qualified exhaled VOCs and urinary concentrations of salbutamol and prednisone showed statistically significant correlations (p<0.01). Conclusion: We have linked exhaled VOCs to urinary detection of salbutamol and OCSs. This merits further development of breathomics into a point-of-care tool for therapeutic drug monitoring. Exhaled volatile organic compounds can be linked to urinary traces of salbutamol and oral corticosteroids. This suggests that breathomics qualifies for development into a point-of-care tool for monitoring asthma drug level changes. http://bit.ly/2Hu4TOf